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Endocrine System

Chapter · June 2018

DOI: 10.1007/978-3-319-47829-6_483-1

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E

Endocrine System functions viz. growth, repair, reproduction, hun-

ger, and survival behavior.
Ashutosh Kumar1,3, Chiman Kumari2,
Sankat Mochan3, Maheswari Kulandhasamy4,
Kishore Sesham3 and Vivek K. Sharma5,6 Introduction
1
Department of Anatomy, All India Institute of
Medical Sciences (AIIMS), Patna, India Animal body has the ductless glands as the dis-
2
Department of Anatomy, Postgraduate Institute tinct organs or cell groups inside an organ or a
of Medical Education & Research (PGIMER), tissue, which exit their secretions called “hor-
Chandigarh, India mones” in the blood circulation to carry to the
3
Department of Anatomy, All India Institute of target destinations. Hormones are involved in the
Medical Sciences (AIIMS), New Delhi, India maintenance of physiological functions involved
4
Department of Biochemistry, Maulana Azad in day to day activities like sleep, feeding, and
Medical College (MAMC), New Delhi, India drinking etc., and also that with prolonged course
5
Department of Physiology, Government Institute of effects like reproduction, growth, aging, immu-
of Medical Sciences (GIMS), Greater Noida, nity, etc. (Kovacs and Ojeda 2012, pp. 1–3).
UP, India These hormone secreting glands are called
6
Department of Physiology, Jawaharlal Institute “endocrine” which literally meant “to secrete
of Postgraduate Medical Education and Research within” indicating their mode of secretion. The
(JIPMER), Pondicherry, India target destinations of the hormones bear the spe-
cific receptors which upon binding induce signal-
ing pathways involved in specific biological
functions. There are eight such major along with
Definition
many minor glands which are grossly conserved
in animal kingdom (including human) and share
It is a physiological functionary comprising of a
similar morphology among mammals. Figure 1 is
network of the ductless glands in the animal body
showing a schema of the major endocrine glands
secreting a chemical messenger, called hormones,
in male and female.
into blood circulation to carry to the target desti-
In general, the “endocrine system” comprises
nations, i.e., various organs and tissues/cells. Hor-
of three parts: a brain part – a nuclei of the hypo-
mones act through the specific receptors
thalamus, a pituitary gland part, and a target endo-
expressed at the target destinations inducing sig-
crine gland. Hypothalamic nuclei secrete
naling pathways involved in the crucial biological
releasing or inhibitory hormones, which either
# Springer International Publishing AG, part of Springer Nature 2018
J. Vonk, T. K. Shackelford (eds.), Encyclopedia of Animal Cognition and Behavior,
https://doi.org/10.1007/978-3-319-47829-6_483-1
2 Endocrine System

Pineal to provide the readers a comprehensive view of

Pituitary the animal “endocrine system,” with a focus in
human.
Thyroid
Thymus

History: A Brief Chronological

Adrenal
Description of the Progress Made in
Pancreas Endocrinology

Earliest descriptions for the endocrine system are

Ovary (female) found about 200 B.C. when Chinese began isolat-
ing sex and pituitary hormones from human urine
and using them for medicinal purposes. Later
Testis (male) descriptions are from the medieval Persia by Avi-
cenna, a legendary scientist, who provided a
detailed account on diabetes mellitus in “The
Canon of Medicine” (c. 1025), describing its clin-
Endocrine System, Fig. 1 Major endocrine glands in the ical features as abnormal appetite, collapse of
human body
sexual functions, and sweet taste of urine.
In 1835 Irish doctor Robert James Graves
stimulate or inhibit anterior pituitary cells to
described a case of goiter with bulging eyes
secrete a stimulatory hormone, which will further
(exophthalmos); the condition was later named
act upon a target endocrine gland like adrenal,
after him as Graves’ disease.
thyroid, or else, which secrete exit hormone
In 1849, Thomas Addison described Addison’s
(s) which will be taken through the blood circula-
disease (also known as primary adrenal deficiency
tion to the target organs or body parts containing
or hypocortisolism). In the same year, Arnold
specific hormonal receptors for action. Exceptions
Berthold, who is regarded as a pioneer in endo-
to this three tier system are some specific cells
crinology, observed that castration had negative
existing inside some organs, or body parts which
effect on male cockerels who did not develop
secrete specific hormones (Kleine and
proper sex-specific characteristics. Later, in 1889
Rossmanith 2016, pp. 269–297; Kumar
Brown-Séquard, a professor at the College de
et al. 2018).
France, reported that self-administration of animal
The endocrine system works in concert with
testes extracts led to enhancements in his physical
the nervous and immune systems which also share
strength, intellectual capacity, and sexual potency
their functionaries (Kovacs and Ojeda 2012,
though it could not be replicated by the others. It
pp. 1–3). The branch of science dealing with the
could not be clarified further until 1904, the year
endocrine system is called “endocrinology,”
Bouin and Ancel reasoned that some secretion
which is now a well-developed branch enjoying
from the Leydig cells is involved in the develop-
the technological advancement for the investiga-
ment of the male characteristics which were later
tory and diagnostic tools in the field.
named testosterone. Pure, crystalline testosterone
Being a physiological functionary “endocrine
was extracted not until 1935.
system” bears the sets of diseases which arise of
In 1889 when Joseph von Mering and Oskar
hyper or hypo function of the specific endocrine
Minkowski described hormonal etiology of the
glands or faults in their brain part regulations or
diabetes, they observed that surgically removing
receptor activation at target site. This chapter is
the pancreas resulted in an increase of blood
dealing with the individual endocrine glands, their
sugar, followed by coma and eventually death.
central and peripheral regulations, implied hor-
In 1891, Murray successfully treated a female
monal mechanisms, and related diseases/disorders
patient with myxedema with thyroid extract.
Endocrine System 3

Case VI Before Insulin Case VI 4 Mos. After

Endocrine System, Fig. 2 Therapeutic effect of insulin available under Creative Commons Attribution Interna-
historically demonstrated in a diabetic girl. (Image credit: tional Licensing)
Welcome Collection, a proprietary of Welcome Trust, UK,

In 1894, Oliver and Schaefer described the hormone (GH) was first described by Evans
presence of epinephrine in extracts from the adre- and Long.
nal medulla. In1922 Banting and Best discovered insulin.
In 1902 William Bayliss and Ernest Starling in Insulin showed a magical effect on the health of
a unique experiment showed that acid instilled the diabetes patients for whom otherwise no cure
into the duodenum induced secretion in pancreas, was available until then (Fig. 2). No later, Eli
even after removing any nervous connections Lilly, a chemist and owner of an American phar-
between the two organs. maceutical company, started mass production of
Nayliss and Starling discovered the hormone insulin (Fig. 3).
secretin in 1903 and also used the first the term In 1962 Sutherland a renowned pharmacist
“hormones” to indicate such chemical reported that the action of epinephrine is mediated
messengers. by secondary messengers like cyclic adenosine
In 1909, MacCallum and Voetlin stated an monophosphate (cAMP). It was a landmark dis-
association between calcium metabolism and the covery which unraveled the mechanism of the
parathyroid glands. action of hormones.
In 1913, Farmi and Von den Velden treated
diabetes insipidus with posterior pituitary
extracts.
Evolutionary and Developmental Basis
In 1921 Otto Loewi first brought the idea of
neurohormones and that year only growth
Most animals with well-developed nervous/circu-
latory systems essentially have an endocrine
4 Endocrine System

Endocrine System, Fig. 3 An advertisement for Lilly Insulin (McCormick). (Image credit: Truman Library)

system. The endocrine system of vertebrates con- mesoderm, ectoderm); hence, the type of endo-
sists of glands and diffuse cell groups scattered in crine product is determined by the tissue layer a
epithelial tissues. Endocrine glands develop from gland originated in. Glands of ectodermal and
all three germinal tissue layers (endoderm, endodermal origin produce peptide and amine
Endocrine System 5

hormones; but mesodermal-origin glands secrete The lower most part of this brain structure projects
steroid or lipid hormones (Sadler and Langman into the pituitary (infundibular) stalk making pos-
2015; Kleine and Rossmanith 2016, terior or neurohypophyseal part of the pituitary
pp. 347–353). gland. The specific nuclei groups of hypothala-
mus involved in the secretion of hormones are
described below along with the functions.
Classification of Endocrine Glands
Function Hypothalamus is the central regulator
Endocrine glands can be classified as central and
of the entire endocrine system. Hypothalamic
peripheral. Central endocrine glands are those
neuronal cells secrete releasing/release inhibiting
which are present within the cranium and are
hormones which further stimulate/inhibit the syn-
part of the brain as hypothalamus, pituitary and
thesis of stimulating hormones from the anterior
pineal glands. The other glands existing outside
pituitary. Chiefly, arcuate nucleus of the tuberal
the cranial premises are called peripheral. Endo-
region, and also some nuclear groups in preoptic
crine glands also can be classified as primary and
and supraoptic regions, which control the secre-
secondary endocrine organs. Primary endocrine
tion of hormones from the anterior pituitary, or the
organs have the only function to secrete hormones
supraoptic and paraventicular nuclei (PVN) of
(Table 1a), but secondary endocrine organs are
supraoptic region of the hypothalamus which
primarily meant for the other biological functions
secrete oxytocin and vasopressin and
and also secrete hormones to support and sustain
corticotrophic releasing hormone (CRH) consti-
their primary functions (Table 1b). In secondary
tute endocrine part of the hypothalamus. Arcuate
endocrine organs, only specific cell groups or
and other hypothalamic nuclei controlling hor-
tissue components would be devoted for the hor-
monal secretion form the anterior pituitary send
monal secretion. Pancreas, though merits to be a
their axons to the median eminence
primary endocrine organ by definition, it is only
(hypothalamic extension which forms stalk of
partly endocrine, as it has only a specific cell
the pituitary gland) and emit their secretions
group (Islets of Langerhans) dispersed along
which get collected in the portal venous capil-
whole length of organ (mainly tail part) which is
laries present there and through the portal veins
endocrine, rest of the pancreas is exocrine –
reach to the anterior pituitary. Contrastingly, oxy-
secretes enzymes meant for digestive functions
tocin and vasopressin are synthesized by the
which exit through ducts. Similarly, hypothala-
supraoptic and paraventricular nuclei of the hypo-
mus though considered as a primary endocrine
thalamus, respectively, though are released at the
organ, only neurons in the specific nuclear groups
posterior pituitary or neurohypophysis where
are endocrine. Table 1 enlists animal endocrine
their axons are ending. Hypothalamic endocrine
glands, exiting hormones, and their major
function is regulated by the instructions from the
functions.
higher cortical centers and also through the feed-
back received from the different hierarchical
levels of the endocrine systems which are under
Endocrine Glands: Brief Anatomy and
the hypothalamic control (Kovacs and Ojeda
Hormone-Related Functions
2012, pp. 116–148, Kleine and Rossmanith
2016, pp. 269–297). Hypothalamic endocrine reg-
Primary Endocrine Organs
ulation is further discussed in this chapter in sec-
tion “Endocrine System: Physiological
Hypothalamus
Regulations.”
Structure Hypothalamus is the basal part of the
diencephalon (its upper part is called thalamus)
making the floor of the third ventricle of the brain.
 6

Endocrine System, Table 1 Animal endocrine glands, hormones, and their major functions
Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
(a) Primary endocrine organs
Hypothalamus Pituitary
Corticotropin- Paraventricular nuclei Stimulates release of ACTH and Adrenocorticotropic Anterior pituitary Stimulates synthesis and release
releasing hormone (PVN) B-endorphin from anterior hormone (ACTH) of glucocorticoids
(CRH) pituitary
Gonadotropin- Preoptic area; anterior Stimulates release of FSH and Follicle-stimulating Anterior pituitary Stimulates development of
releasing hormone hypothalamus LH from anterior pituitary hormone (FSH) ovarian follicles and secretion
(GNRH) of estrogens; stimulates
spermatogenesis
Luteinizing hormone- Nuclei; medial basal Stimulates release of LH from Growth hormone Anterior pituitary Mediates somatic cell growth
releasing hormone hypothalamus (rodents and anterior pituitary (GH)
(LHRH) primates); arcuate nuclei
(primates)
Somatostatin (growth Anterior periventricular Inhibits release of GH and TSH Luteinizing hormone Anterior pituitary Stimulates Leydig cell
hormone-inhibiting nuclei from anterior pituitary inhibits (LH) development and testosterone
hormone) release of insulin and glucagon production in males; stimulates
from pancreas corpora lutea development and
production of progesterone in
females
Melanotropin-release Arcuate nuclei Inhibits the release of MSH Melanocyte- Anterior pituitary Affects memory; affects skin
inhibitory factor (no evidence of this peptide in stimulating hormone color in amphibians
(Dopamine) humans) (MSH)
Neuropeptide Arcuate nuclei Regulation of energy balance Prolactin (PRL) Anterior pituitary Many actions relating to
Y (NPY) reproduction, water balance,
etc.
Neurotensin Arcuate nuclei Regulation of energy balance Thyroid-stimulating Anterior pituitary Stimulates thyroid hormone
hormone or secretion
thyrotropin (TSH)
Orexin A and B Lateral hypothalamic area Regulation of energy balance/ Oxytocin Posterior pituitary Stimulates milk letdown and
food intake uterine contractions during birth
Thyrotropin-releasing Paraventricular nuclei Stimulates release of TSH and Vasopressin or Posterior pituitary Increases water reabsorption in
hormone (PVN) PRL from anterior pituitary antidiuretic hormone kidney
ADH or AVP
Endocrine System
Histamine Tuberomamillary nucleus Increases wakefulness, prevent Pineal gland
(also from mast cells) sleep
Kisspeptin Arcuate nucleus Acting on the receptors present Melatonin Pinealocytes Affects reproductive and
in the anterior pituitary circadian control of bodily
regulates synthesis/secretion of functions
reproductive hormones
Endocrine System

Adrenal gland Thyroid/parathyroid

Mineralocorticoids Thyroxine or Follicular cells Regulate oxidation and basic
tetraiodothyronine metabolic rates in tissue;
(T4) learning associated
Triiodothyronine neuroplasticity
(T3)
Aldosterone Zona glomerulosa of Sodium retention in kidney Calcitonin (CT) C-cells of thyroid Lowers serum Ca2+ levels
adrenal cortex
11- Zona glomerulosa of Sodium retention in kidney Parathyroid Parathyroid gland Stimulates bone resorption;
Deoxycorticosterone adrenal cortex hormone (PTH) increases serum Ca2+ levels
(DOC)
Glucocorticoids
Cortisol Zona fasciculata and Increases carbohydrate Pancreas (Islet cells of Langerhans)
(hydrocortisone)/ z. reticularis of adrenal metabolism; antistress hormone
corticosterone cortex Increased carbohydrate Glucagon a-cells Glycogenolysis in liver
metabolism; antistress hormone Insulin b-cells Glucose uptake from blood;
glycogen storage in liver
Dehydroepiandro- Zona reticularis of adrenal Weak androgen; primary Somatostatin d-cells Inhibits insulin and glucagon
sterone DHEA cortex secretory product of fetal secretion
adrenal cortex Pancreatic Peripheral cells of Effects on gut in
polypeptide (PP) pancreatic islets pharmacological doses
Epinephrine or Adrenal medulla Glycogenolysis in liver;
adrenaline (EP) increases blood pressure
Norepinephrine or Adrenal medulla Increases blood pressure
noradrenaline (NE)
Ovary
Estrogen Follicles (also in brain Uterine and other female tissue Progesterone Corpora lutea, Uterine development;
regions like hippocampus, development Enhances placenta mammary gland development;
hypothalamus, prefrontal cognition, neuroprotective maintenance of pregnancy
cortex, amygdala)
Inhibin . . .. . .. . ..
7

(continued)
 8

Endocrine System, Table 1 (continued)

Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
Testes
Androstenedione Leydig cells Male sex characters Testosterone Leydig cells Spermatogenesis; male
secondary sex characters
Dihydrotestosterone Seminiferous tubules and Male secondary sex characters
(DHT) prostate
(b) Organs with secondary endocrine function
Organ Hormone Major functions Organ Hormone Major functions
Lung Leukotrienes (LT) Long-acting Multiple organs Prostaglandins E1 and Contraction/relaxation of
bronchoconstrictors E2 PGE1 and PGE2 smooth muscle cells in vessels,
aggregation/disaggregation of
platelets, sensitization to pain
(and other actions)
Heart Atrial naturetic factor Regulation of urinary sodium Multiple organs Klotho Enhances cognition, protects
(Atrial myocytes) (ANF) excretion against aging
Thymus Thymosin, thymulin and Proliferation/differentiation of Skin Cholecalciferol Modified to form Vit. D
(Thymocytes) thymopoietin lymphocytes
Kidney Renin Stimulates release of Liver Insulin like growth Stimulates bodily growth
aldosterone factor (IGF-1)
Calcitriol Helps absorption of Ca2+ Angiotensinogen Raises blood pressure
Erythropoietin Induces absorption of red blood Thrombopoietin Causes increase in platelets
cells in bone marrow
Endocrine System
Skeleton FGF23 Inhibits production of calcitriol Hepcidin Blocks release of iron into body
and increases phosphate fluids
excretion
Osteocalcin Increase insulin secretion Gut
Adipose tissue Leptin Promotes satiety signals in the Bombesin Neurons and Hypothermic hormone;
Endocrine System

brain endocrine cells of gut increases gastrin secretion

Adiponectin Reduces insulin resistance Cholecystokinin Duodenum and CNS Stimulates gallbladder
(CCK) contraction and bile flow;
affects memory, eating behavior
Placenta Gastric inhibitory Duodenum Inhibits gastric acid secretion
polypeptide (GIP) G-cells of midpyloric Increases secretion of gastric
Gastrin glands in stomach acid and pepsin
antrum
Chorionic Placenta LH-like functions; maintains Gastrin-releasing GI tract Stimulates gastrin secretion
gonadotropin (CG) progesterone production during peptide (GRP)
pregnancy
Chorionic Placenta Acts like PRL and GH Vasoactive intestinal Small intestine (also in Inhibits gastric acid secretion
somatomammotropin peptide (VIP) central and enteric and increases intestinal
or placental lactogen nervous system, and secretion of water and
(CS) nerve terminals) electrolytes; a neurotransmitter/
neuromodulator in CNS/ENS
Serotonin GI tract and blood Maintain mood, sleep, appetite,
platelets (also a and digestion. Regulate bowel
neurotransmitter in function and movements
brain)
9
10 Endocrine System

Endocrine System, Neurosecretory cells

Fig. 4 Hypophyseal portal
circulation
Hypothalamus

Capillary plexus

Hypophyseal artery Portal veins

Endocrine cells
Adenohypophysis

Pituitary vein Neurohypophysis

Pituitary Gland Pineal Gland

Structure Pituitary gland is the master controller Structure Pineal is a minute pine cone like gland
of all peripheral primary endocrine glands. This located at the rear end of the diencephalon. The
gland is located in the hypophyseal fossa (also cellular elements of the gland are pinealocytes
called pituitary fossa) which is placed in the center (approx. 95%) and neuroglia cells, and it is
of middle cranial fossa of base of the skull. Embry- densely filled with afferent nerve terminals. The
ological derivation of this gland is unique. Poste- gland is highly vascular and rich in sympathetic
rior half of the gland is the extension of the innervations.
hypothalamus hence neural and is called neurohy-
pophysis. The neurohypophysis contains the axons
Function Pineal gland secretes (by pinealocytes)
terminals of the neurons supraoptic and PVN
a serotonin-derived photoactive hormone melato-
nuclei of the supraoptic region of the hypothala-
nin which helps regulate circadian rhythm of the
mus. Anterior part of the gland is derived from the
body (to regulate the sleep and wakefulness) in
evagination of the oral ectoderm infront of the
concert with the biological clock situated in the
buccopharyngeal membrane and is called adeno-
supra-chiasmatic nuclei (SCN) of the hypothala-
hypophysis. Most of the pituitary hormones are
mus. It is also a known powerful antioxidant.
secreted from the adenohypophysis part except
Melatonin secretion is regulated by light exposure
oxytocin and vasopressin or antidiuretic hormone
and its intensity and shows a rhythmic secretion,
(ADH) which are secreted from the neurohypoph-
being low during the daylight hours and high
ysis part (Kovacs and Ojeda 2012, pp. 116–171).
during dark periods.
Melatonin is also believed to be involved in
Function The hypothalamic releasing or inhibi- sexual development and reproductive functions
tory hormones regulate the synthesis of trophic (blocks secretion of LH and FSH), thermoregula-
hormones from the anterior pituitary through tion, cellular metabolism, and also in immune
hypophyseal portal system (Fig. 4). Posterior pitu- function. Though there is little evidence in
itary hormones oxytocin and vasopressin regulate human that the pineal gland plays a significant
hemodynamic status of the body. Oxytocin is also role in the neuroendocrine regulation of reproduc-
involved in induction of the delivery and ejection tion during either puberty or adulthood, in season-
of breast milk in female (Kovacs and Ojeda 2012, ally breeding animals, such as sheep and
pp. 148–171). Both of the hormones have effect hamsters, melatonin secretion is said to be
on animal social behavior, memory, and learning, influenced by the day length and thus gating
especially oxytocin, which is also called social reproduction as a function of the season (Kleine
molecule (Kumar et al. 2018). and Rossmanith 2016, pp. 243–244).
Endocrine System 11

T4 T4

5’Deiodinase

T3 MIT Tg I0
T3 Hydrolysis I0
I– I– Tg
Tg
DIT
I– I0 Tg
I0
NIS
I– I0
TPO
+
2Na 2Na+ Single
thyroid
cell
Blood
vessel Thyroid
follicle

Endocrine System, Fig. 5 Synthesis of Thyroid hormones. I: ionized iodine; I0: oxidized iodine; Tg: thyroglobulin;
TPO: thyroid peroxidase

Thyroid Gland is exclusive to and an essential component of the

thyroid hormones. The term “iodine” here refers
Structure Thyroid gland is situated in the neck to the elemental form of the iodine (I) which will
extending from C5 to T1 vertebrae and is related get assimilated in the hormones in the iodide form
with laryngeal cartilages and upper tracheal rings. (I
). Ingested iodine is absorbed through the small
It is a butterfly-like structure having two lobes and intestine and transported in the plasma to the
a connecting isthmus that lies in front of 2–4th thyroid, where it is concentrated, oxidized, and
tracheal rings. The lobes lie on either side of the then incorporated into thyroglobulin (Tg) to
larynx and trachea and whole gland is covered by form intermediate mono and diad (MIT and DIT)
pretracheal fascia. In some individuals, an extra and later final and active triad (T3) and tetra (T4)
smaller lobe of thyroid called pyramidal lobe may forms of thyroid hormones in the thyroid follicles,
be present, which may extend from the isthmus up and is stored there for a variable period (Fig. 5).
to the hyoid bone. Further, Tg base of the thyroid hormones undergo
proteolysis releasing T3 and T4 into the circulation
Function Thyroid gland secretes hormones Tri- to be carried by specific binding proteins to target
iodothyronine (T3) and Tetra-iodothyronine or tissues. The synthesis of T4 is about 4 times more
Thyroxine (T4) which are involved in the regula- than T3. Its vast influence is mediated through
tion of the basic metabolic rate of the body differential expression of hormone receptor iso-
(influencing physiological functioning of almost forms in tissues and conversion of thyroxine (T4)
each cell and the organ). Thyroid hormones are to triiodothyronine (T3), by the enzyme
secreted from the lining epithelial cells of the 50 -deiodinase (Fig. 5). The thyroid hormone
follicles which further go iodination in the colloid secretion is controlled by thyrotropin-releasing
filled in the lumen of the follicles (Fig. 5). Iodine hormone (TRH) from hypothalamus and thyroid
12 Endocrine System

stimulating hormone (TSH) from anterior pitui- Gonadotrophins The adrenal cortex secretes
tary along with nutritional signals like availability many male sex hormones, including DHEA,
of the iodine and carrier molecules, and also by DHEA sulfate (DHEAS), androstenedione, and
the environmental factors like radiation, chemical 11-hydroxyandrostenedione, and also small quan-
exposure, drugs, and temperature. Calcitonin is a tities of the female sex hormones progesterone
small polypeptide hormone secreted by the para- and estrogen. Androgens secreted from the adre-
follicular or “C” cells of the thyroid. Calcitonin nal go extra-adrenal conversion to testosterone.
decreases blood calcium and increases blood These androgens have a role in early development
phosphate level by suppressing the osteoclast of the male sex organs in childhood. They also
activity in bones and increasing the amount of mediate secondary sexual characteristics during
calcium excreted in urine (Kleine and Rossmanith puberty in the both sexes. ACTH from anterior
2016, pp. 269–297). pituitary has a physiological stimulatory effect on
androgen release by the adrenal.
Parathyroid
Mineralocorticoids Aldosterone accounts for
Structure The small glands (about 50 mg), two most of the mineralocorticoid activity, with some
each side, are normally found on the posterior contribution from glucocorticoids. The concentra-
aspect of the lobes of thyroid gland. tion of aldosterone in blood exhibits diurnal var-
iation, and the secretory rate is generally
Function Parathyroid gland secretes parathyroid 150–250 mg/day. Aldosterone promotes sodium
hormone (PTH) that controls calcium and phos- reabsorption and potassium excretion by the tubu-
phate homeostasis in the body. Effect of PTH on lar epithelial cells of the collecting and distal renal
blood calcium and phosphate levels is opposite of tubules thus way maintaining normal osmolality
calcitonin for which it is known as an antagoniz- and water balance in blood. Reabsorption of
ing hormone. sodium is followed by passive absorption of
water, leading to an increase in the extracellular
Adrenal Gland fluid volume with minimal change in the plasma
sodium concentration.
Structure Adrenal gland is a small gland located
on the top of each kidney enclosed in renal fascia Glucocorticoids Most of the glucocorticoid
(alternative name for this is suprarenal gland). It activity comes from cortisol, with corticosterone
has cortical and medullary parts which secrete having a minor contribution. The normal blood
steroid and amine hormones respectively. The cortisol concentration averages 12 mg/dL, with an
cortex is further differentiated into pars average secretory rate of 15–20 mg/day. Cortisol
glomerulosa, fasiculata, and reticularis. Central secretion from adrenal gland is the output hor-
medullary part contains chromaffin and ganglion mone in HPA axis, and also it is the chief stress
cells of neural crest origin. hormone in body. Other functions of cortisol are
like counteracting insulin secretion, stimulating
Functions Its cortical and medullary parts gastric-acid secretion, reducing bone formation,
secrete distinct hormones which are involved in and functioning as a diuretic. Cortisol also con-
maintaining important physiological functions. tributes to the maintenance of various homeostatic
actions, like blood pressure, immune system,
Cortical Hormones The pars glomerulosa, metabolism of protein, carbohydrate, and fat,
fasiculata, and reticularis secreting sex steroids and anti-inflammatory action. Its secretion is con-
or gonadotrophins, mineralcorticoids, and gluco- trolled by the hypothalamo-pituitary-adrenal
corticoids or cortisol in order. All cortical hor- (HPA) axis, which follows a circadian rhythm
mones are steroid compounds derived from and also gets influenced by exposure to the light
cholesterol. and hours of the sleep (vice versa it regulates
Endocrine System 13

sleep) (Longo 2015, Chapter 399; Kleine and inhibin and relaxin suppress). Relaxin also relaxes
Rossmanith 2016, pp. 339–346). Its regulation the hip ligaments before delivery of the child.
through HPA axis and neural and molecular Estrogens also have effect on the physiological
basis of rhythmic secretion are further discussed processes other than reproduction such as bone
in this chapter in section “Endocrine System: metabolism/remodeling, nervous system matura-
Physiological Regulations.” tion, and endothelial responsiveness. Estrogen
also brings pubertal changes in female like breast
Medullary Hormones The chromaffin and gan- development and enlargement and maturation of
glion cells in the medulla secrete epinephrine/ the uterus, ovaries, and vagina. Estrogen also
adrenalin and norepinephrine/noradrenaline and works in concert with growth hormone and
in minute amount dopamine. These hormones insulin-like growth factor I (IGF-I) to produce a
are secreted into the bloodstream as a result of growth spurt and stimulates the maturation of
direct stimulation by acetylcholine release from chondrocytes and osteoblasts, which ultimately
the sympathetic nerves. Preganglionic sympa- leads to epiphyseal fusion. Until midpuberty,
thetic nerve fibers reach to the chromaffin cells estrogen begins to exert a positive feedback on
of the adrenal medulla without synapsing any- gonadotropin-releasing hormone (GnRH) secre-
where else. These hormones are responsible for tion, leading to the progressive increase of LH
the maintenance of cardiac output, physiological and FSH production, culminating in the LH
vascular resistance, and stress response (Kleine surge, ovulation, and the initiation of the men-
and Rossmanith 2016, pp. 269–297). strual cycle. In the adult female, estrogen plays a
critical role in maintaining the menstrual cycle
Ovary (Kovacs and Ojeda 2012, pp. 194–238, Kleine
and Rossmanith 2016, pp. 269–297).
Structure Ovary is the female gonad located in
the pelvis one on each side at the terminal end Testes
(fimbria) of the uterine tube. A single follicle is the
endocrine unit of the ovary. Each follicle contains Structure Testis is the male gonad which in con-
a germ cell/oocyte at the core surrounded by an trast to the female gonad, along with the external
inner and an outer layer composed of granulosa genitalia presents in the perineal region, present
cells and theca cells, respectively. bilaterally enclosed in scrotal sac.

Function It secretes the hormones which are Function It chiefly secretes testosterone which is
essential for the maintaining functions and health necessary for the gametogenesis and also devel-
of their reproductive organs. Ovary chiefly opment and maintenance of the male reproductive
secretes estrogen and progesterone which are, system and male sexual behavior. Higher center
respectively, responsible for the initiation and regulation of testosterone synthesis is much sim-
maintenance of the pregnancy, and also secretes pler than the female sex hormones due to absence
androstenedione and testosterone in slighter of a defined cyclic period in male. The male sex
amount which can get converted to estrogen hormones secreted from adrenal gland make addi-
with aromatization. Estrogen also shows a termi- tional source of this hormone through conversion.
nal surge which induces secretion of the oxytocin
which in turn would initiate uterine contraction to Pancreas (Islet Cells)
facilitate delivery of the child. Ovary also secretes
minor nonsteroidal hormones as activin, inhibin, Structure Islet cells of the pancreas which are
and relaxin. Nonsteroidal ovarian hormones have dispersed among the exocrine acini as clusters
a contribution in regulating production of steroid constitute endocrine part of this organ. Islet cell
hormones though chief regulation is by LH and clusters are more abundant towards rear part of the
FSH by anterior pituitary (activin enhances, and organ with highest density in the tail.
14 Endocrine System

Function Islet cells secrete three types of the the pregnancy, syncytial cells of the trophoblast
hormones: alpha cells secrete glucagon, beta secrete human chorionic gonadotrophin (HCG),
cells insulin, and delta cells somatostatin, respec- which helps to maintain corpus luteum until pla-
tively, which are crucial for the normal metabolic centa takes the action of synthesizing progester-
functions of the body. Insulin and glucagon con- one. HCG also inhibits LH like gonadotrophins to
trol the two opposite aspects of glucose metabo- stop further ovulations and to help sustain preg-
lism, glycogenesis and glycogenolysis, nancy. This hormone is excreted in the maternal
respectively, in consequent control concentration urine in initial months of the pregnancy and is
of glucose in blood. Insulin is also involved in the used as a gestational indicator. Another hormone
metabolism of many other energy storing bio- secreted by the placenta is somatomammotropin
molecules which finally reduce blood glucose (placental lactogen), which is a growth hormone
level. like substance, providing fetus a priority on mater-
nal glucose and inducing maternal glucose syn-
Organs/Tissue Components with Secondary thesis hence making the mother functionally
Endocrine Function diabetic during pregnancy. It also helps growth
Certain animal organs contain a tissue component of the breast in mother (Sadler and Langman
or specific cell groups with endocrine functions 2015, pp. 116–117).
(Table 1b). Below is being provided a brief
descriptions of such endocrine structures and
Thymus
their functions.
Structure The thymus is a double lobed struc-
Placenta
ture located in the upper anterior part of chest
directly behind sternum. It has an outer zone
Structure Placenta is an endocrine organ of
called cortex and an inner zone called medulla.
pregnancy. All female mammals other than mono-
Histologically, the organ is composed of two
tremes and marsupials (most) bear placenta during
types of cell called lymphocytes and reticular
pregnancy. Placenta is implanted in the uterine
cells. The cortex bears the immature T cells
wall, where it receives nutrients and oxygen
which migrate to the medulla in order to mature
from the mother’s blood and passes out excretory
(Standring 2016, pp. 1362–1365).
products. It is a disc like structure. Uniquely, it has
maternal and fetal components both providing a
physical link between the two. Maternal and fetal Function Thymus produces hormones like thy-
components are derived from uterine decidua mosin (alpha 1), thymulin, and thymopoietin,
(functional layer of the endometrium which is which have been stated to circulate through
shed during parturition) and chorionic frondosum blood and to act on both prothymocytes and
(an outer trophoblast shell and inner chorionic mature T-cells in the periphery which helps to
plate made of extraembryonic mesoderm), respec- maintain commitment and functions of these
tively (Sadler and Langman 2015, p. 112). It is the cells. The hormones produced by the thymus pro-
fetal component, especially the syncytial layer of mote the maturation of the T cells prior to their
the trophoblast cells, which is endocrine, and release into the blood. Once these thymic lympho-
secretes hormones to sustain pregnancy. cytes (or T cells) have fully matured in the thy-
mus, they migrate to the lymph nodes in the body
Functions Placenta secretes progestins (mainly and guard against invader microorganisms or liv-
progesterone) along with the corpus luteum. ing or nonliving foreign particles causing dis-
It also secretes estrogen (especially weaker eases, a biological function called immune
estriol) which inhibit the LH along with the pro- surveillance (Kleine and Rossmanith 2016,
gesterone to help sustain pregnancy and induce pp. 269–297; Standring 2016, pp. 1362–1365).
growth of the breast. During initial 2 months of
Endocrine System 15

Adipose Tissue which has an opposite effect on hemodynamic

Adipose tissue secretes several hormones. These balance in the body (Kleine and Rossmanith
hormones are mainly involved in lipid metabo- 2016, pp. 269–297).
lism and storage. Adiponectin – a hormone syn-
thesized by adipose cells – appears to reduce Gastrointestinal Tract
cellular insulin resistance and to protect blood The mucosa of the GI tract, mainly the stomach
vessels from inflammation and atherosclerosis. and small intestine, contains specialized cell
Leptin, synthesized by the adipose cells, acts as which secrete hormones meant to help in the
an indicator of satiety. It is released in response to digestion. Like, G-cells in the stomach secrete a
food and acts on the neuronal regions dealing with peptide hormone, gastrin, in response to disten-
the energy intake and expenditure (Kleine and sion caused by entering food that stimulates the
Rossmanith 2016, pp. 269–297). release of hydrochloric acid from other cells. Sim-
ilarly, secretin, a peptide hormone, is secreted by
Skin the small intestine in response to the acidic chyme
The skin cells synthesize inactive form of vitamin released from stomach. Secretin stimulates the
D3, cholecalciferol from cholesterol when release of bicarbonate from the pancreas, antago-
exposed to ultraviolet radiation. Cholecalciferol nizes acidic chyme, and also inhibits the further
is converted to an intermediate in liver, which secretion of hydrochloric acid by stomach
further is converted to calcitriol – the active form mucosa. Cholecystokinin (CCK) is another pep-
of vitamin D3, in kidney. Vitamin D is important in tide hormone released from small intestine which
a variety of physiological processes, including induces the secretion of digestive enzymes from
intestinal calcium absorption and immune system pancreas and also the release of bile from the
function (Kleine and Rossmanith 2016, gallbladder. Intestinal hormones are also involved
pp. 269–297). in glucose metabolism, like gastrin inhibitory
peptide-1 (GIP-1) and glucagon like peptide-
Skeleton 1(GLP-1) secreted from the small intestine induce
Bone cells secrete Fibroblast growth factor secretion of insulin (Kleine and Rossmanith 2016,
23 (FGF23). Its action is to inhibit the formation pp. 269–297; Kumar et al. 2018).
of calcitriol from vitamin D3 and to increase phos-
phorus excretion from kidney. Osteocalcin, from Liver
the osteoblasts, induces insulin secretion from The endocrine function of liver is highly involved
pancreas and also promotes its responsiveness in metabolic regulation of the digestive nutrients.
on the peripheral tissues (Longo 2015, chapter It synthesizes various hormones such as insulin-
423). like growth factor (somatomedin),
angiotensinogen, thrombopoietin, and hepcidin.
Heart IGF-1 has insulin-like effects as its name sug-
Specialized cells in the atrium wall secrete the gests, and it can bind to the insulin receptor. Its
peptide hormone atrial natriuretic peptide (ANP) actions are mediated through a same named tyro-
in response to distension caused by increased sine kinase receptor which presents on the surface
blood volume or pressure. ANP has a role in of almost all cells and is the stimulus for growth in
maintaining hemodynamic status of the body. It the body. Angiotensinogen by the action of
reduces sodium reabsorption and, in turn, enzyme renin secreted from the kidney gets
decreases accompanied water reabsorption from converted to angiotensin which is a substrate of
the urinary filtrate in the kidney, bringing down Renin-Angiotensin-Aldosteron System (RAAS)
the total blood volume. It also has an inhibitory maintaining hemodynamic balance in the body.
effect on the renin secretion from the specialized Angiotensin also causes vasoconstriction (Kleine
cells of the kidney tubules, hence initiation of the and Rossmanith 2016, pp. 269–297). Hepcidin is
renin-angiotensin-aldosterone system (RAAS) small peptide hormone majorly synthesized in the
16 Endocrine System

liver. It is chief regulator of the extra cellular

excretion of the iron in the body (Gressner and
Gressner 2018).
HO

Cholesterol O
Kidneys
Certain cells of kidney secrete hormones which O
are crucial for hemodynamic and electrolyte bal- O
ance in the body. A decline in blood flow which is Pregnenolone Progesterone
detected at the glomerular filtration system HO

induces release of the enzyme renin, which in

O
turn switches on the RAAS stimulating the Cortisol Aldosterone
DHEA
reabsorption of sodium and water leading to
OH
increase in blood flow and blood pressure. The HO
OH
kidneys regulate blood calcium levels through the
production of calcitriol from vitamin D3, which is HO
O Testostero
released in response to the secretion of PTH. Low
ne (and Estradiol (and other
oxygen level in circulation induces synthesis of other estrogens)
erythropoietin (EPO) from kidney which in turn androgens)
would stimulate the production of red blood cells
Endocrine System, Fig. 6 Cholesterol derivations of the
(erythrocytes) in the bone marrow, thereby
lipid hormones
increasing oxygen delivery to tissues
(Mukoyama and Nakao 2005).
Endocrine System, Table 2 Neurohormones
Corticotropin-releasing Thyrotropin-releasing
Hormones Hormone (CRH) Hormone
Gonadotropin-releasing Histamine
Hormone (GNRH) Vasopressin or antidiuretic
Types and Structure Luteinizing hormone- Hormone)
Hormones are mostly proteins, but some are also releasing ADH or AVP
peptides, amines, or steroids. The protein, peptide, Hormone (LHRH) Oxytocin
or amine hormones are water soluble, but steroid Somatostatin (growth Norepinephrine
Hormone-inhibiting Dopamine
hormones are lipid soluble. Lipid-soluble hor- Hormone) Serotonin
mones act slow, but their effects last longer than Melanotropin-release Melatonin
water soluble hormones (Kleine and Rossmanith Inhibitory factor B-endorphin
2016, pp. 11–17; Kumar et al. 2018). Lipid hor- (dopamine) Agouti-related protein
Neuropeptide Y (NPY) (AGRP)
mones have a common molecule of origin as Neurotensin Estrogen
cholesterol (Fig. 6). Most of the hormones are Orexin A and B
secreted by peripheral organs or specific tissue Reproduced with permission from Hormones and Behav-
components. Some hormones are synthesized ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
inside the brain which are called “neurohor- nition and Behavior, Springer Nature
mones” (Table 2). Neurohormones also include
some of the sex hormones (estrogen, progester-
one, and testosterone) which are also synthesized These hormones attach to the receptors present
by cortical neurons (Ish et al. 2007). on the surface of target cells creating the
hormone-receptor complex, in turn engaging a
Mechanisms of Action G-protein dependent secondary messenger path-
Protein, peptide, and amine hormones (except way (like cAMP, cGMP, Diacylglycerol, Ca++,
thyroid hormones) are water soluble, hence can- etc.,) to induce protein kinases/phosphorylases
not cross through the cell membrane directly. related to specific biological events. Steroid
Endocrine System 17

a Hormone
Protein, peptide, b
amine hormones Steroid and Thyroid
receptor
hormones
complex
Cell surface receptor

Molecular
Secondary transporters
messenger

Protein
enzymes++

Coding of mRNAs

Protein synthesis

Endocrine System, Fig. 7 Mechanisms of action (a) Hormones and Behavior, Kumar A. et al., 2018, Encyclo-
Protein, peptide, and amine hormones (b) Steroid and pedia of Animal Cognition and Behavior, Springer Nature)
thyroid hormones. (Reproduced with permission from

hormones are lipid soluble, hence can cross on the metabolic processes involved. Metabolic
through the cell membranes. They directly reach processes which need urgent response, such as
nucleus tagged with transporters or binding pro- blood glucose or calcium homeostasis, are usually
tein present in the cell cytoplasm, where they set controlled by peptide hormones (also epinephrine),
free from the carrier molecule and attach to the but processes for which response is slow, such as
nuclear receptors (binding sites) at DNA promoter pubertal development or basic metabolic rate, are
regions for the genes assigned for forming specific controlled by steroid hormones and thyroid hor-
proteins (Fig. 7) (Kleine and Rossmanith 2016, mones. Electrolyte homeostasis requires intermedi-
pp. 263–267; Kumar et al. 2018). ate response speed and is regulated by peptide and
Thyroid hormones, though chemically amine, steroid hormones both (Kleine and Rossmanith
are exception to the group. Their three dimen- 2016, pp. 263–267).
sional structure resembles that of the steroid hor-
mones, hence can enter the cell and reach to the
Hormone Secretion, Transport, and
specific nuclear receptors with the help of specific
Degradation
transporters present at the cell membrane
The blood level of a hormone is determined by its
(facilitated diffusion) and in the cell cytoplasm.
rate of secretion and its circulating half-life. After
Hormones are biologically active in very minute
protein processing, peptide hormones are stored in
amount which get usually measured in micrograms
secretory granules, from where are later released
(mg, 10
6 g), nanograms (ng, 10
9 g), or picograms
into the circulation. The stimulus for hormone
(pg, 10
12 g). Hormone-Receptor interactions for
secretion may be a releasing factor or neural signal
all categories of hormones are highly specific,
that induces rapid changes in intracellular calcium
reversible, and satiable and follow a threshold limit
concentrations, leading to secretory granule
for the maximal biological response (i.e., follow
fusion with the plasma membrane and release of
normal distribution curve). Also, there is differential
the hormones. In contrast, steroid hormones dif-
purposing of the category of hormones depending
fuse into the circulation as they are synthesized
18 Endocrine System

Endocrine System, Table 3 BBB free regions in brain

Circumventricular organs
1. Organum vasculosum of lamina terminalis
2. Subfornical organ
3. Subcommissural organ
4. Median eminence (hypothalamus)
5. Intermediate lobe of pituitary gland
6. Posterior pituitary
7. Pineal gland
8. Area postrema (4th ventricle)
Reproduced with permission from Hormones and Behav-
ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
nition and Behavior, Springer Nature

hence their secretory rates are closely aligned with

rates of the synthesis.
Hormone transport and degradation determine
the speed with which a hormonal signal may
decay. Some hormonal signals are short decaying
(e.g., somatostatin), whereas others are longer-
lived (e.g., TSH). An understanding of circulating
hormone half-life is necessary for the proper phys-
iologic hormone replacement (Longo 2015, chap-
ter 399). Endocrine System, Fig. 8 Feedback regulations at cen-
tral endocrine axes

Crossing Blood Brain Barrier (BBB)

Transport of a hormone through blood brain bar- hormones – presenting a unique opportunity for
rier (BBB) depends on whether it is water or lipid neuron-hormone interactions.
soluble. Steroid hormones are lipid soluble, hence
can easily pass to and fro through the BBB (the
peripherally synthesized hormones enter brain Endocrine System: Physiological
and those synthesized inside brain reach to periph- Regulations
ery), but protein, peptide, amine, and other hor-
mones which are water soluble can do it with help Central Endocrine Axes and Hormonal
of the transporters/binding proteins only. Trans- Homeostasis
port of the lipid insoluble hormones is a saturable/ The endocrine system is governed by the central
rate limited process due to exhaustion of the trans- axes which essentially connects three components
porters/binding proteins (Banks 2012; Kumar of the system: a brain component – a nuclei of the
et al. 2018). hypothalamus, anterior part of the pituitary gland,
Certain of the hormone synthesizing brain and any of the endocrine glands as adrenal,
regions, called circumventricular organs, are gonads, or thyroid. Each axis is regulated by the
devoid of a blood brain barrier (BBB) which feedback cycles (Fig. 8) (Kleine and Rossmanith
facilitates the release of the stored hormones in 2016, pp. 299–338; Kumar et al. 2018). Table 4
the blood (Table 3) (Kumar et al. 2018). mentions the central axes, their essential compo-
These BBB-free regions are also the site for nents, and secreted hormones.
receiving peripherally released hormones. These Central endocrine axes run from hypothalamus
brain regions contain receptors for the peripheral to adrenal, gonads, or thyroid via anterior part of
Endocrine System 19

Endocrine System, Table 4 Central endocrine axes in the animals (including human)
Target
endocrine
Hypothalamic component/ organ/
Name hormone Pituitary component/hormone hormone
Hypothalamic- Paraventricular nucleus (PVN)/ Adrenocorticotrophs, anterior pituitary/ Cortisol/
pituitary- adrenal corticotrophin releasing adrenocorticotrophin hormone (ACTH) cortisone
(HPA) axis hormone (CRH)
Hypothalamic- Paraventricular nucleus Thyrotrophs, anterior pituitary/thyroxine Thyroxine
pituitary-thyroid PVN/thyrotrophin releasing stimulating hormone (TSH) 3 and 4
(HPT) axis hormone (TRH) (T3 and T4)
Hypothalamic- Arcuate nucleus/gonadotrophin Gonadotrophs, anterior pituitary/follicle Estrogen/
pituitary-gonadal releasing hormone (GnRH) stimulating hormone (FSH)/leutinizing progesterone
(HPG) axis hormone (LH)

pituitary (adenohypophysis). Hypothalamus in prolactin from the anterior pituitary and also sets
association with anterior pituitary and adrenal auto-inhibition of its own secretion (Macleod
gland constitutes HPA axis – which bears an et al. 1981).
influence on most of the neurophysiological func-
tions and is crucial for the neuroendocrine adap- Paracrine and Autocrine Regulation
tation to the stress. A parallel axis connecting Paracrine regulation refers to factors released by
hypothalamus and anterior pituitary to gonads one cell that act on an adjacent cell in the same
(testis in male and ovary in female) constitutes tissue, such as somatostatin secretion by pancre-
HPG axis which regulates reproductive functions. atic islet cells inhibits insulin secretion from
In HPG axis, releasing/inhibitory hormones are nearby cells. Autocrine regulation states the
secreted from specific hypothalamic nuclei action of a factor on the same cell from which it
which induce synthesis/release of stimulating/ is produced, such as IGF-I acts on the cells that
luteinizing hormones from anterior pituitary produce it to regulate its secretion.
which in turn induce synthesis/release of sex hor-
mones from the gonads. The peripheral endocrine Circadian Control of Endocrine Functions
glands and their central regulatory centers work in SCN and PVN nuclei of hypothalamus regulate
coordination in an attempt to maintain a state of circadian release of hormones. Pineal gland is also
functional equilibrium or physiological homeo- known to maintain circadian release of melatonin
stasis in the body (Kleine and Rossmanith 2016, which depends on exposure of the organism to the
pp. 299–338). light. The circadian release of any hormone from
Feedback regulation also occurs for endocrine the hypothalamic and pineal nuclei is affected by
systems that do not involve the central axes, for the duration and intensity of the light exposure.
example, calcium feedback on PTH, glucose inhi- The SCN and other hypothalamic nuclei are
bition of insulin secretion, and leptin feedback on connected to the retina – screening portal of the
the hypothalamus. light, through bidirectional retinohypothalamic
Uniquely, prolactin a hormone secreted from connections. Pineal gland nuclei are also
the anterior pituitary essential for the control of connected to this circuitry through to and fro
the lactation in female and many other functions channels. Control of circadian rhythm through
has only two components in its regulatory axis- hypothalamic nuclei is a complex biological pro-
(hypothalamo-prolactin axis) which does not con- cess which is genetically determined and con-
tain an inter-gland feedback loop. The dopamine served among species (Tsang et al. 2014;
secreted from the tubero-infundibular nuclei of Andreani et al. 2015). The molecular repertoire
the hypothalamus is inhibitory to the secretion of maintaining circadian rhythms (Table 5) are not
20 Endocrine System

Endocrine System, Table 5 Molecular repertoire IGF-1 and melatonin, and sex hormones like
of SCN DHEA, estrogen, and progesterone. Decline of
Brain and muscle ARNT like protein-1 (Bmal1) the melatonin may play an important role in the
Clock (or Npas2 in neuronal tissue) loss of circadian rhythms with aging. Sex
Cryptochrome (cry) 1,2 hormone-binding globulin is reported to increase
Period (per)1,2,3 with age in both sexes. Levels of some hormones
E-box may also increase, like LH and FSH, and pancre-
Retinoid-related orphan receptor (Ror) a, b, l atic polypeptide and gastrin (but not other gut
Rev-Erb a, b
hormones). For some hormones, their levels
Chrono
remain near normal with aging, these are thyroid
Casein kinase 1 (ck1) d, e
(except T3, which is reduced possibly due to
Reproduced with permission from Hormones and Behav-
ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
decrease conversion from T4). Parathyroid hor-
nition and Behavior, Springer Nature mone shows an increase that may be due to
decreased renal excretion. Adrenal cortical hor-
mones like glucocorticoid and mineralocorticoid
present only in the endocrine organs but in many show higher serum concentrations with aging
organs and tissues, which together create a com- though the target organ for mineralocorticoid
plex molecular network system with a central activity (kidney), however, becomes less respon-
command from SCN (Hughey and Butte 2016). sive. For adrenal medullary hormones like epi-
Cortisol, the HPA axis output hormone, also nephrine and norepinephrine, their baseline
follows circadian rhythm, with its peak secretion serum concentrations increase with aging though
in the morning at 8 AM with lesser serum values stimulable increases in both (as percentages of the
along the day, with minimum at 4 PM. basal concentrations) show a decrease. The circa-
A dysregulation of circadian synthesis/release of dian patterns for the hormones showing diurnal
the hormones is implicated in metabolic syn- variation like cortisol, norepinephrine, and
dromes and neuroendocrine disorders including growth hormone are altered in aged.
stress-induced psychiatric disorders and sleep dis- In female, fall of the female sex hormones
orders (Kleine and Rossmanith 2016, (estrogen and progesterone) is marked by meno-
pp. 299–338; Kumar et al. 2018). pause near the age of 45 years with rise of LH and
FSH (LH initially may show a fall at commence-
ment of menopause). In males, there is a gradual
Endocrine-Nervous-Immune Cross-Regulation fall of testosterone and increase of LH and FSH
Endocrine system is an autonomous but not a with aging called andropause. Insulin secretion is
completely independent physiological unit. It impaired and insulin resistance increases with
has noted cross regulation with the nervous and age. Levels of androgens in female and estrogen
immune system – which meant that hormones in male may not show much change with aging
interact with the neuropeptides/neurotransmitters (Chahal and Drake 2007).
and immune cell derived cytokines. Evidence
suggests that interaction between these systems
is bidirectional and a dysregulation of it implicates Endocrine Disorders
in etiogenesis of the diseases like metabolic and
psychiatric disorders (Kelley 1988). Each endocrine organ has specific disorders
which may alter functions of the related physio-
logical systems. Certain of the endocrine diseases/
Effects of Aging on Endocrine System disorders present as the syndrome involving many
organs. Endocrine disorders can result from dys-
Most hormone levels decrease with aging. Salient function originating in the peripheral endocrine
hormones which decrease with aging are GH, gland itself (primary disorders) or under stimulation
Endocrine System 21

or overstimulation by the central regulators of an investigations used for in vitro determination of

endocrine axis as anterior pituitary, or hypothalamic hormones or their receptors are immunocyto-
nuclei (secondary disorders). The disorders can chemistry (ICC), autoradiography, in situ hybrid-
result in hormone overproduction (hyperfunction) ization, and blotting. Medical imaging techniques
or underproduction (hypofunction). Rarely, endo- (like PET scan and f-MRI) which reveal organ
crine disorders (usually hypofunction) occur activation during certain actions or behaviors,
because of reduced responses from the target site paired with endocrine manipulations or monitor-
receptors (Longo 2015, chapter 399; Kleine and ing, can provide important information (Fusani
Rossmanith 2016, pp. 357–376). 2017). For human cases, taking patient history
Endocrine disorders may also happen from and clinical examination is the first thing to be
exogenous or self-administration of a hormone, done for an endocrine disorder, which would pave
or due to a blockade in the regulatory axis for an the way which tests should be conducted to reach
endocrine gland (such as HPA axis), or in a diagnosis. Hematology and urinalysis provide
response of a diseased state (Longo 2015, chapter important information in diagnosing endocrine
399). disorders. Other investigations are available to
Hypofunction of a peripheral endocrine gland test the function of specific endocrine glands.
can be caused by congenital (like a genetic disor- Medical imaging like CT and MRI scans, sonog-
der resulting from deletion of a gene), or acquired raphy, and scintillation counting are useful for
disorders (like autoimmune and vascular disor- detecting change in the size of endocrine glands
ders, tumors, infections, toxins, or hormone and the presence of tumors or cysts. Karyotyping
receptor hypofunction). Some hormones require for the chromosomal errors, or genotyping, or
conversion to an active form after secretion from sequencing for mutation analysis, and
the synthesizing gland, which may happen in genomewide association study for single nucleo-
some other glands, a dysfunction of the organ tide polymorphisms (SNPs) or copy number var-
where activation has to take place, may result in iations (CNVs) are also done for the disorders
hormonal hypofunction. For example, inactive where a genetic basis is speculated (Fusani 2017;
form of Vitamin D is synthesized in the liver Kumar et al. 2018).
which requires further modification in kidney
and skin, respectively, to become active, a disease Common Therapeutic Approaches
of kidney or skin may result in hypofunction of Control of the hypersecretion (surgical removal,
vitamin D. Primary hyperfunction of endocrine radio or chemosuppression, or using a pharmaco-
glands generally results from hyperplasia or neo- logical agent as the antagonist) and replacement or
plasia of the gland. Other reasons for this can be correction of the deficiency (by pharmacological or
ectopic production of a hormone from a different dietary means, or treating the causes) are the main
tissue as may happen in cancers and autoimmune stream approaches for treating the endocrine dis-
diseases (as in hyperthyroidism of Graves’ dis- orders (Longo 2015, chapter 399–409). Recently,
ease). Table 6 provides a detailed list of endocrine gene-based therapeutic approaches have shown
diseases/disorders with anatomical and functional promises for this where a genetic basis is known.
abnormality for each. Known gene-based approaches are either correc-
tion of the faulty genes through genomic editing
Commonly Used Investigations or gene supplementation or using antisense oligo-
The concentration of hormones in blood or serum nucleotides against the targeted genes. Gene ther-
in the living animal can be investigated with the apy is considered more suitable for correcting the
immunoassays (radio-, enzyme-, and monogenic endocrine disorders like GH defi-
fluorescence-immunoassay) and more recently ciency or familial hypercholesterolemia, though
high-performance liquid chromatography newer advances in gene-based therapy have also
(HPLC) and mass-spectrometry combined with raised hope for the multifactorial diseases like
gas chromatography (MS–GC). The general diabetes mellitus or endocrine cancers, and
Endocrine System, Table 6 Major endocrine disorders, their causes, clinical features, diagnostic investigations, and management
22

Glands Disorders Pathology/causes Signs and symptoms Diagnostic investigations Management

Hypothalamus Trauma Symptoms caused by Hormone analysis, Hormone replacement
deficiency of pituitary, neuroimaging
Tumors adrenal or gonadal hormones. Hormone analysis, Surgical removal of the
Symptoms are also specific to neuroimaging tumor. radiotherapy, hormone
the etiology replacement
Kallmann syndrome Genetic mutation Hormone analysis,Genetic Gene correction, hormone
screening replacement
Anorexia Nervosa and Hormone analysis Hormone replacement
Bulimia Nervosa
Prader-Willi Symptoms caused by Hormone analysis Hormone replacement
syndrome deficiency of pituitary,
Inflammatory and adrenal, or gonadal Hormone analysis, Hormone replacement
vascular diseases, hormones. Symptoms are
malnutrition, also specific to the etiology
infection, radiation
Central precocious Early release of GnRH from Early onset of puberty GnRH stimulation testing GnRH analogue therapy
puberty hypothalamus may be due to
brain injury or a pituitary
tumor
Pituitary Cushing’s disease Excessive production of Weight gain, high blood Blood hormone analysis, Surgical removal of tumor/
ACTH due to some tumor pressure, thinning of the skin, neuroimaging medication
easy bruising, etc.
Acromegaly Excessive production of GH Abnormally increased height Blood hormone analysis, Surgical removal of tumor/
due to some tumor neuroimaging medication
Pituitary growth Due to low secretion of GH Decreased height Blood hormone analysis, Surgical removal of tumor/
failure neuroimaging medication
Hypogonadotr opic Low LH and FSH Delayed puberty Blood hormone analysis, Surgical removal of tumor/
hypogonadism Leading to low secretion of neuroimaging medication
testicular/ovarian hormones
Pituitary masses Excessive production of some Large masses may compress Blood hormone analysis, Surgical removal of tumor/
hormones, like in surrounding tissue, erode into neuroimaging medication
prolactinoma bone, or produce excess
hormone
Hypopituitarism Surgery, radiation treatments, Nonspecific, including Blood hormone analysis, Surgical removal of tumor/
large pituitary tumors, weakness, fatigue, and neuroimaging hormone replacement
Endocrine System
 bleeding or loss of blood dizziness, headache,
supply occasional loss of
consciousness
Central diabetes Damage to the pituitary gland Intense thirst even after Urine and blood tests, water Medication (desmopressin a
insipidus (or hypothalamus) disrupting drinking fluids (polydipsia), deprivation test. synthetic ADH analogue),
Endocrine System

the normal production, and excretion of large Investigations for underlying management of waterloss,
storage and release of ADH amounts of urine (polyuria), causes electrolyte imbalance and
Due to surgery, a tumor, an electrolyte imbalance water loss
illness (such as meningitis),
inflammation or a head injury
or an inherited genetic
disorder (in children), of an
unknown cause
Thyroid and Hyperthyroidism Excessive production of Restlessness, agitation, Blood hormone analysis, Medication, radioactive
parathyroid thyroid hormones due to anxiety, tremors, weight loss, tests for specific antibodies iodine therapy
autoimmune conditions sweating, rapid heart rate,
(Graves disease) or intolerance to heat, and,
inflammation frequent bowel movements
Hypothyroidism Low production of thyroid Tiredness, feeling cold, Thyroid hormone analysis, Thyroid hormone
hormones due to autoimmune weight gain, dry skin, increased blood TSH replacement
conditions or inflammation, constipation, and swelling
surgery, radiation, drug (edema) of the face or ankles
induced
Thyroiditis Excess/low production of Sign and symptoms of hyper/ Testing for the thyroid Depending on the hormonal
thyroid hormones due to hypo thyroidism peroxidase (TPO) antibody in analysis
autoimmune conditions the blood/thyroid hormone
((Hashimoto’s thyroiditis) or analysis
infections, hypersensitivity
Tumors Benign and cancerous Pressure in the neck, FNAC (biopsy), radioisotope Surgical removal, radioactive
hoarseness of the voice, or scan iodine therapy
difficulty in swallowing or
breathing, metastatic
symptoms
Hyperparathyroidism Excess parathyroid hormone Increased blood calcium Blood hormone analysis Calcium monitoring, surgery
(PTH) in the blood, caused by levels can cause symptoms of
tumorous growth in tiredness, poor concentration,
parathyroid gland low mood, bone pain, and
stomach or abdominal
symptoms
23

(continued)
Endocrine System, Table 6 (continued)
24

Glands Disorders Pathology/causes Signs and symptoms Diagnostic investigations Management

Adrenal Hypercortisolism Excess production of adrenal High blood pressure, weight Blood and/or urine testing Medication, surgical removal
hormone cortisol secondary to gain, thinning of the skin, of the tumor
Cushing’s syndrome or an easy bruising, poor wound
adrenal tumor healing
Hyperaldosteronism Excess production of adrenal Low potassium in the blood Blood test, adrenal vein Medication, surgical removal
hormone aldosterone due to a and high blood pressure sampling of the tumor
tumor or nodular disease resistant to treatment
Adrenal insufficiency Reduced hormone secretion Weakness, weight loss, Blood hormone analysis, Hormone replacement
from the adrenal gland, dizziness, and sometimes screening for specific
resulting in deficiency of all abdominal pain, nausea, and antibodies
adrenal hormones, including vomiting
cortisol and aldosterone.
Reasons may be autoimmune
destruction of the adrenal
gland (Addison’s disease),
bleeding into the adrenal
glands, or infections, such as
tuberculosis
Adrenal masses Mostly benign and rarely Symptoms of Ultrasound, CT and MRI, Clinical monitoring, surgery
cancerous tumors. May hyperaldosteronism and histopathology
produce excess adrenal corticosolism
hormones
Ovary Ovarian insufficiency Ovaries either do not develop, Symptoms of low estrogen Blood hormone analysis Hormone replacement
(sometimes called or are damaged hence no can develop in many, but not
premature longer function normally all: hot flashes, night sweats,
menopause) poor sleep, and vaginal
dryness. Infertility and the
loss of the beneficial effects
of estrogen and progesterone
Polycystic ovary Small cysts in the ovaries, Irregular menstrual periods, Blood tests for sex hormone, Ovulation induction by
syndrome (PCOS) increased amount of loss of fertility, increased hair ultrasound medication, surgery
androgens produced by the growth on the face, chest, or
ovaries abdomen, acne, and a
tendency toward weight gain
and insulin resistance
(diabetes)
Endocrine System
Testis Low testosterone Due to testicular trauma, Reduced energy, mood, Blood hormonetest/clinical Testosterone replacement
levels in men radiation or chemotherapy for strength, and libido radiological evaluation
certain types of cancer,
infection or loss of blood
supply to the testes
Primary testicular Genetic causes Reduced energy, mood, Blood hormone analysis/ Testosterone replacement
Endocrine System

hypogonadism strength and libido, infertility genetic screening

Androgen Genetic causes Female phenotypic features Blood hormone analysis/ Management for functional,
insensitivity with male genetic makeup, genetic screening sexual, and psychological
syndromes infertile issues
Pancreas (islet Diabetes mellitus Dysfunction of insulin Insulin resistance is related to Blood test for glucose level, For type 1 diabetes, synthetic
cells) production/secretion (type 1), the metabolic changes of late HbAc, insulin insulin must be administered
or the target cells’ pregnancy, and the increased by injection or infusion.
responsiveness to insulin insulin requirements may For type 2, life style changes
(type 2) lead to IGT or diabetes and insulin
Gestational diabetes mellitus
(GDM)
Neuroendocrine Sign and symptoms depend Serum hormone and analysis Hormone replacement,
tumors like on the hormone involved Genetic screening, CT, MRI surgery, medication
insulinoma,
gastrinoma,
glucagonoma,
carcinoid tumor, etc.
Multiple Multiple endocrine Primary Serum calcium and PTH, Genetic screening for
endocrine neoplasia I and II hyperparathyroidism, adrenal hormone estimation mutations, surgery/
organs (MEN I and MEN II) hypercalcemia, (elevated levels of serum medication
hypophosphatemia, increased calcium and intact
secretion of epinephrine/ parathyroid hormone)
norepinephrine CT, MRI
Polyglandular Mutations, inherited disorder Sign and symptoms depend Serum hormone analysis Hormone replacement
autoimmune (Pga) on the hormone involved Genetic screening
syndromes
25
26 Endocrine System

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