HORMONES

1. Definition
 Hormones are chemical messengers secreted by specialized glands (endocrine
glands) or cells, which travel through the bloodstream (or act locally) to regulate
physiological processes in target tissues/organs.
 They act at very low concentrations but produce significant biological effects.
 Hormones are distinct from enzymes: hormones regulate, while enzymes catalyze
reactions.
 The study of hormones and their actions is called Endocrinology.
2. Origin
Hormones are secreted by endocrine glands (ductless glands), neurosecretory cells, and
some specialized tissues. Main sources include:
a) Hypothalamus – secretes releasing and inhibiting hormones (e.g., TRH, CRH,
GnRH, GHRH, somatostatin).
b) Pituitary gland – secretes growth hormone (GH), prolactin, ACTH, TSH, LH, FSH.
c) Thyroid gland – thyroxine (T4), triiodothyronine (T3), calcitonin.
d) Parathyroid glands – parathyroid hormone (PTH).
e) Pancreas (Islets of Langerhans) – insulin, glucagon, somatostatin.
f) Adrenal glands – adrenal cortex (cortisol, aldosterone, androgens); adrenal medulla
(adrenaline, noradrenaline).
g) Gonads – ovaries (estrogen, progesterone), testes (testosterone).
h) Placenta – human chorionic gonadotropin (hCG), human placental lactogen (hPL).
i) Other tissues – kidney (erythropoietin), stomach (gastrin), heart (atrial natriuretic
peptide), adipose tissue (leptin).
3. Structure
Hormones are classified according to their chemical nature, which determines their
solubility, transport, receptor type, and mechanism of action:
1. Peptide/Protein hormones
o Short chains (peptides) or long chains (proteins).

o Examples: insulin, glucagon, GH, prolactin, PTH.

o Water-soluble, stored in vesicles, act via membrane receptors and second

messengers (cAMP, IP3/DAG).
2. Steroid hormones
o Derived from cholesterol.

o Examples: cortisol, aldosterone, testosterone, estrogen, progesterone.

 o Lipid-soluble, not stored in vesicles but synthesized on demand.

o Act via intracellular/nuclear receptors, altering gene transcription.

3. Amino acid derivatives

o Derived from tyrosine or tryptophan.

o Examples: thyroxine (T4), adrenaline, melatonin.

o Some are water-soluble (catecholamines), others lipid-soluble (thyroid

hormones).
4. Fatty acid derivatives (eicosanoids)
o Derived from arachidonic acid.

o Examples: prostaglandins, thromboxanes, leukotrienes.

o Mostly act locally (paracrine/autocrine).

4. General Function of Hormones

Hormones maintain homeostasis and coordinate body activities. Their major functions
include:
 Metabolism regulation – insulin lowers blood glucose, glucagon raises it, thyroid
hormones increase basal metabolic rate.
 Growth and development – GH, IGF-1, thyroid hormones, sex steroids.
 Reproduction – estrogen, progesterone, testosterone, LH, FSH, prolactin.
 Stress response – adrenaline and cortisol increase energy supply during stress.
 Water and electrolyte balance – ADH regulates water reabsorption, aldosterone
regulates sodium and potassium balance, PTH regulates calcium.
 Immune modulation – cortisol suppresses immune activity.
 Digestive regulation – gastrin, secretin, CCK.
5. Control of Hormones
Hormone secretion is tightly controlled by several mechanisms:
1. Hypothalamic-pituitary axis – releasing hormones from the hypothalamus control
pituitary hormones, which then control peripheral endocrine glands (e.g., TRH →
TSH → Thyroid hormones).
2. Nervous system – direct innervation of glands (e.g., sympathetic nerves stimulate
adrenal medulla to release adrenaline).
3. Chemical signals – e.g., plasma glucose regulates insulin/glucagon; plasma calcium
regulates PTH/calcitonin.
 4. Circadian rhythms – melatonin (night secretion), cortisol (peaks in the morning).
5. Physiological demand – pregnancy increases estrogen, progesterone, and prolactin
secretion.
6. Feedback Mechanisms
Feedback ensures hormones remain within physiological levels:
1. Negative feedback (most common):
o Increased hormone levels inhibit further secretion.

o Example: High cortisol inhibits CRH (hypothalamus) and ACTH (pituitary).

2. Positive feedback (rare):

o Hormone secretion stimulates more secretion until a specific event occurs.

o Example: Estrogen surge before ovulation stimulates LH surge; oxytocin

stimulates uterine contractions which enhance further oxytocin release during
childbirth.
3. Feedforward control:
o Anticipatory regulation before a change occurs.

o Example: Insulin secretion at the sight/smell of food.

7. Other Regulatory Factors

 Age: Hormone secretion varies (e.g., GH high in childhood, sex hormones rise at
puberty, decline in old age).
 Gender: Different patterns in males and females (testosterone vs.
estrogen/progesterone cycles).
 Stress: Physical/emotional stress increases cortisol, adrenaline, and noradrenaline.
 Drugs/chemicals: Steroids, thyroid drugs, alcohol, caffeine influence hormone
secretion.
 Disease states: Diabetes (insulin deficiency), hypothyroidism (low T3/T4), Cushing’s
syndrome (excess cortisol).
 Nutrition: Adequate iodine needed for thyroid hormone; protein deficiency affects
GH and insulin.
 Sleep and circadian rhythm: Growth hormone secreted mainly at night, cortisol
follows daily rhythm.
A). HYPOTHALAMUS HORMONES
secretes releasing and inhibiting hormones (e.g., TRH, CRH, GnRH, GHRH, somatostatin).
1. Thyrotropin-Releasing Hormone (TRH)
Definition
A tripeptide hypothalamic hormone that stimulates release of TSH and prolactin from the
anterior pituitary.
Origin
 Secreted by neurons in the paraventricular nucleus of the hypothalamus.
Structure
 Very small peptide: 3 amino acids (pyroglutamyl-histidyl-proline amide).
General Function
 Stimulates secretion of TSH from thyrotrophs → thyroid hormones (T3, T4).
 Stimulates secretion of prolactin from lactotrophs.
Control
 Cold exposure increases TRH release (especially in infants).
 Stress can decrease secretion.
Feedback
 Negative feedback by thyroid hormones (T3, T4) at both hypothalamus and pituitary
levels.
Other Regulatory Factors
 Sleep-wake cycles affect secretion.
 Drugs like dopamine agonists can indirectly suppress TRH-induced prolactin release.
2. Corticotropin-Releasing Hormone (CRH)
Definition
A peptide hormone that stimulates secretion of ACTH from the anterior pituitary.
Origin
 Secreted by neurons in the paraventricular nucleus of the hypothalamus.
Structure
 41 amino acid peptide.
General Function
  Stimulates secretion of ACTH from corticotrophs.
 Indirectly increases cortisol secretion from adrenal cortex.
 Plays a major role in stress response.
Control
 Stress (emotional, physical, hypoglycemia, trauma) strongly increases CRH release.
 Circadian rhythm: peak secretion in early morning.
Feedback
 Negative feedback by cortisol at both hypothalamus (↓CRH) and pituitary (↓ACTH).
Other Regulatory Factors
 Chronic stress may dysregulate CRH and ACTH secretion.
 Vasopressin (ADH) can potentiate CRH action.
3. Gonadotropin-Releasing Hormone (GnRH)
Definition
A hypothalamic peptide hormone that regulates release of LH and FSH.
Origin
 Secreted by neurons in the preoptic area and arcuate nucleus of hypothalamus.
Structure
 Decapeptide (10 amino acids).
General Function
 Stimulates release of LH and FSH from gonadotrophs.
 Regulates reproduction (ovulation, spermatogenesis).
Control
 Secreted in pulsatile fashion (frequency/amplitude determines LH vs. FSH
predominance).
 Continuous exposure leads to receptor downregulation and suppression of LH/FSH.
Feedback
 Negative feedback: Sex steroids (estrogen, progesterone, testosterone) inhibit GnRH
release.
 Positive feedback: High estrogen levels just before ovulation trigger GnRH surge →
LH surge.
Other Regulatory Factors
 Kisspeptin neurons play a crucial role in regulating GnRH secretion.
 Nutrition and stress influence GnRH activity (undernutrition suppresses GnRH).
 Puberty onset marked by increased GnRH pulsatility.
4. Growth Hormone–Releasing Hormone (GHRH)
Definition
A hypothalamic peptide hormone that stimulates secretion of growth hormone (GH).
Origin
 Secreted by neurons in the arcuate nucleus of the hypothalamus.
Structure
 44 amino acids peptide (active form often truncated to 40 or 37 aa).
General Function
 Stimulates GH release from somatotrophs.
 Promotes growth, metabolism, and IGF-1 production.
Control
 Hypoglycemia, stress, exercise, and deep sleep stimulate GHRH release.
 Somatostatin (inhibitory) counterbalances GHRH action.
Feedback
 Negative feedback via IGF-1 and GH itself, which inhibit further GHRH secretion.
Other Regulatory Factors
 Ghrelin (from stomach) works synergistically with GHRH to stimulate GH.
 Age: GHRH activity declines with age → reduced GH secretion.
5. Somatostatin (Growth Hormone–Inhibiting Hormone, GHIH)
Definition
A hypothalamic inhibitory hormone that suppresses secretion of GH, TSH, and several
gastrointestinal hormones.
Origin
 Produced by periventricular nucleus of hypothalamus.
 Also secreted by pancreatic delta cells and gastrointestinal mucosa.
Structure
  14 amino acid peptide (main active form).
 Exists also as a longer 28 amino acid form.
General Function
 Inhibits GH secretion (main function in pituitary).
 Inhibits TSH release from pituitary.
 Inhibits insulin, glucagon, gastrin, and other GI hormones (in pancreas/GIT).
Control
 High blood glucose, increased GH, and IGF-1 stimulate somatostatin release.
Feedback
 Acts in a negative feedback loop with GH and IGF-1.
Other Regulatory Factors
 Stress, exercise, and sleep influence its secretion.
 Therapeutic analogs (e.g., octreotide) are used to treat acromegaly and GI tumors.
B). PITUITARY GLAND
Secretes growth hormone (GH), prolactin, ACTH, TSH, LH, FSH.
The pituitary gland is a small, pea-sized endocrine gland located at the base of the brain, just
below the hypothalamus, in a bony cavity called the sella turcica.
It is often called the “master gland” because it controls and regulates the activity of many
other endocrine glands in the body (such as the thyroid, adrenal glands, ovaries, and testes)
through the hormones it secretes.
The gland has two main parts:
1. Anterior pituitary (adenohypophysis) – Produces and releases hormones such as
growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), thyroid-
stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing
hormone (LH).
2. Posterior pituitary (neurohypophysis) – Stores and releases hormones made by the
hypothalamus, such as antidiuretic hormone (ADH/vasopressin) and oxytocin.
Anterior Pituitary Hormones
1. Growth Hormone (GH / Somatotropin)
Definition
A protein hormone secreted by the anterior pituitary that promotes growth, cell reproduction,
and metabolism.
Somatostatin is a peptide hormone that acts mainly as an inhibitory regulator in the
endocrine system, nervous system, and digestive system.
Origin
 Secreted by somatotrophs in the anterior pituitary.
 Stimulated by hypothalamic GHRH; inhibited by somatostatin.
Structure
 Single-chain polypeptide, ~191 amino acids.
 Belongs to the somatotropin/prolactin family.
General Function
 Stimulates growth of bone, muscle, cartilage (via IGF-1 from the liver).
 Promotes protein synthesis.
 Increases lipolysis (fat breakdown).
 Reduces glucose uptake (anti-insulin effect → hyperglycemia tendency).
 Important in childhood and adolescence.
Control
 Hypothalamic GHRH stimulates release.
 Somatostatin inhibits release.
 Ghrelin (from stomach) also stimulates GH secretion.
Feedback
 Negative feedback via IGF-1 (insulin-like growth factor-1), which inhibits GH release
at both hypothalamus and pituitary.
Other Regulatory Factors
 Exercise, sleep (deep sleep), stress, and hypoglycemia increase GH secretion.
 Obesity and aging reduce GH secretion.
2. Prolactin (PRL)
Definition
A protein hormone involved mainly in lactation and reproductive functions.
Origin
 Secreted by lactotrophs of the anterior pituitary.
 Controlled primarily by inhibitory signals (dopamine).
Structure
 Single-chain polypeptide (~199 amino acids).
 Structurally similar to GH.
General Function
 Promotes breast development during pregnancy.
 Stimulates milk production after childbirth.
 Modulates immune response.
 Inhibits reproductive functions (by suppressing GnRH).
Control
 Dominantly inhibited by dopamine from the hypothalamus.
 TRH can stimulate prolactin release.
Feedback
 Suckling reduces dopamine release, allowing prolactin secretion (positive
neuroendocrine loop).
Other Regulatory Factors
 Stress, pregnancy, and estrogen increase prolactin secretion.
 Hyperprolactinemia may cause infertility and galactorrhea.
3. Adrenocorticotropic Hormone (ACTH / Corticotropin)
Definition
A peptide hormone that stimulates the adrenal cortex to secrete glucocorticoids (cortisol).
Origin
 Secreted by corticotrophs in the anterior pituitary.
 Derived from POMC (proopiomelanocortin).
Structure
 39 amino acids peptide.
General Function
 Stimulates secretion of cortisol (main), and to a lesser extent aldosterone and adrenal
androgens.
 Increases adrenal growth.
 Important in stress response.
Control
 Hypothalamic CRH stimulates secretion.
 Stress and low cortisol increase CRH and ACTH release.
Feedback
 Negative feedback by cortisol on both hypothalamus (↓CRH) and pituitary (↓ACTH).
Other Regulatory Factors
 Circadian rhythm: ACTH highest in early morning.
 Stress (trauma, illness) increases secretion.
4. Thyroid Stimulating Hormone (TSH / Thyrotropin)
Definition
A glycoprotein hormone that regulates the thyroid gland’s secretion of T3 and T4.
Origin
 Secreted by thyrotrophs in the anterior pituitary.
 Stimulated by hypothalamic TRH.
Structure
 Glycoprotein consisting of α and β subunits (β subunit confers specificity).
General Function
 Stimulates thyroid hormone synthesis (T3, T4).
 Promotes thyroid gland growth (trophic effect).
Control
 TRH stimulates secretion.
 Somatostatin and dopamine inhibit secretion.
Feedback
 Negative feedback by thyroid hormones (T3/T4) at both pituitary and hypothalamus.
Other Regulatory Factors
 Cold exposure (especially in infants) increases TRH/TSH secretion.
 Stress can suppress TSH release.
5. Luteinizing Hormone (LH)
Definition
A gonadotropin that regulates gonadal steroid production and reproductive functions.
Origin
 Secreted by gonadotrophs in the anterior pituitary.
 Stimulated by hypothalamic GnRH.
Structure
 Glycoprotein with α and β subunits.
General Function
 In females: Triggers ovulation, stimulates corpus luteum to produce progesterone.
 In males: Stimulates Leydig cells to produce testosterone.
Control
 Pulsatile GnRH release regulates LH secretion.
 Estrogen and testosterone influence secretion.
Feedback
 Negative feedback: Testosterone (in males) and estrogen/progesterone (in females)
suppress LH.
 Positive feedback: High estrogen before ovulation causes LH surge.
Other Regulatory Factors
 Puberty onset increases GnRH → LH secretion.
 Stress and malnutrition suppress LH release.
6. Follicle Stimulating Hormone (FSH)
Definition
A gonadotropin that regulates gametogenesis (egg and sperm development).
Origin
 Secreted by gonadotrophs in the anterior pituitary.
 Stimulated by hypothalamic GnRH.
Structure
 Glycoprotein with α and β subunits.
General Function
 In females: Stimulates growth and maturation of ovarian follicles; promotes estrogen
production.
  In males: Stimulates Sertoli cells to support spermatogenesis and secrete inhibin.
Control
 GnRH regulates secretion.
 Inhibin (from Sertoli cells in males, granulosa cells in females) selectively inhibits
FSH.
Feedback
 Negative feedback: Estrogen, testosterone, and inhibin reduce FSH secretion.
Other Regulatory Factors
 Puberty onset increases FSH secretion.
 Menopause causes persistently high FSH due to loss of ovarian negative feedback.

C). THYROID GLAND HORMONES

Thyroxine (T4) and Triiodothyronine (T3)
Definition
 Thyroxine (T4) and Triiodothyronine (T3) are iodinated amino acid–derived
hormones produced by the thyroid gland.
 They regulate basal metabolic rate, growth, and development.
 T4 is the major circulating form, but T3 is the more active form.
Origin
 Secreted by thyroid follicular cells.
 Synthesized from the amino acid tyrosine and iodine.
 Stored in the thyroid colloid bound to thyroglobulin, then released into circulation
when needed.
Structure
 Both are derived from tyrosine:
o T4 = contains 4 iodine atoms.

o T3 = contains 3 iodine atoms (more potent, shorter half-life).

General Function
 Metabolism: Increases basal metabolic rate by stimulating mitochondrial activity and
oxygen consumption.
  Growth and development: Essential for brain development in infants and skeletal
growth in children.
 Cardiovascular system: Increases heart rate and cardiac output.
 Thermogenesis: Increases heat production.
 Macronutrient metabolism: Enhances carbohydrate absorption, lipolysis, and
protein turnover.
Control
 Controlled by hypothalamic-pituitary-thyroid (HPT) axis:
o TRH (hypothalamus) → stimulates TSH (pituitary).

o TSH → stimulates thyroid hormone synthesis and release.

 Iodine availability is crucial for synthesis.

Feedback
 Negative feedback: Elevated T3 and T4 inhibit TRH (hypothalamus) and TSH
(pituitary).
Other Regulatory Factors
 Iodine intake: Excess or deficiency disrupts thyroid function.
 Drugs/chemicals: Amiodarone, lithium, and antithyroid drugs affect thyroid hormone
synthesis.
 Pregnancy: Increases thyroid-binding globulin, leading to higher total T4/T3 but
normal free hormone levels.
 Circadian rhythm: TSH and thyroid hormones show daily variation.
2. Calcitonin
Definition
A peptide hormone produced by the thyroid that regulates calcium homeostasis by lowering
blood calcium levels.
Origin
 Secreted by parafollicular cells (C cells) of the thyroid gland.
Structure
 A 32 amino acid peptide hormone.
General Function
 Reduces blood calcium levels by:
 o Inhibiting osteoclast activity (↓ bone resorption).

o Increasing calcium deposition in bone.

o Enhancing renal calcium excretion.

 Plays a minor role in calcium regulation compared to parathyroid hormone (PTH).

Control
 Stimulated by high plasma calcium levels.
 Not significantly regulated by the hypothalamic-pituitary axis.
Feedback
 Negative feedback: As calcium levels fall, calcitonin secretion decreases.
Other Regulatory Factors
 Calcitonin secretion can be influenced by gastrointestinal hormones (e.g., gastrin).
 Its physiological role in adults is relatively minor but more important in childhood
(bone growth) and pregnancy (protecting maternal skeleton).
 Clinically, calcitonin is a tumor marker for medullary thyroid carcinoma.
✅ So in summary:

 T3 and T4 regulate metabolism, growth, and development through the HPT axis with
negative feedback.
 Calcitonin regulates calcium by opposing PTH, though less critical in adults.

D). PARATHYROID HORMONE (PTH)

1. Definition
 Parathyroid hormone (PTH) is a peptide hormone secreted by the parathyroid glands.
 It plays a central role in calcium and phosphate homeostasis by increasing blood
calcium levels.
 It is sometimes called parathormone.
2. Origin
 Secreted by the chief cells of the parathyroid glands (small glands usually located
behind the thyroid gland).
 The human body typically has four parathyroid glands.
3. Structure
  84 amino acid polypeptide.
 Synthesized as a larger precursor (prepro-PTH → pro-PTH → mature PTH).
 Rapidly degraded in circulation (half-life ~2–4 minutes).
4. General Function
PTH is the major regulator of blood calcium and phosphate:
1. Bone:
o Stimulates osteoclast activity (indirectly via osteoblasts) → increases bone
resorption → releases calcium and phosphate into blood.
2. Kidneys:
o Increases calcium reabsorption (distal tubules).

o Decreases phosphate reabsorption (proximal tubules) → increases phosphate

excretion (phosphaturia).
o Stimulates 1α-hydroxylase enzyme → activates Vitamin D (calcitriol).

3. Intestine (indirect effect):

o Via calcitriol, PTH increases intestinal absorption of calcium and phosphate.

Overall effect: ↑ Blood calcium, ↓ Blood phosphate.

5. Control
 Plasma ionized calcium is the primary regulator (via calcium-sensing receptors,
CaSR, on chief cells).
o Low Ca²⁺ → stimulates PTH secretion.

o High Ca²⁺ → suppresses PTH secretion.

 Mild reduction in magnesium stimulates PTH, but severe hypomagnesemia inhibits

secretion.
6. Feedback
 Negative feedback:
o Elevated blood calcium directly inhibits PTH release.

o Calcitriol (active vitamin D) suppresses PTH synthesis and secretion.

7. Other Regulatory Factors

 Phosphate levels: High serum phosphate stimulates PTH secretion (because
phosphate binds calcium, lowering free Ca²⁺).
 Vitamin D (calcitriol): Inhibits PTH synthesis.
  Age: PTH levels may rise with aging.
 Pathology:
o Hyperparathyroidism → hypercalcemia, bone resorption, kidney stones.

o Hypoparathyroidism → hypocalcemia, tetany, seizures.

In summary:
 PTH is secreted by parathyroid chief cells.
 It increases blood calcium, decreases blood phosphate.
 Controlled mainly by plasma calcium (negative feedback).
 Works in close coordination with calcitonin (thyroid C cells) and vitamin D
(calcitriol).
E). PANCREATIC HORMONES (ISLETS OF LANGERHANS)
1. Insulin
Definition
A peptide hormone that lowers blood glucose by promoting uptake and storage of
glucose, fats, and amino acids.
Origin
 Secreted by β-cells of the pancreatic islets of Langerhans.
Structure
 Composed of two polypeptide chains (A-chain = 21 amino acids, B-chain = 30
amino acids) linked by disulfide bonds.
 Synthesized as preproinsulin → proinsulin → insulin.
 Stored in granules with C-peptide.
General Function
 Carbohydrate metabolism: Increases glucose uptake (via GLUT4 in muscle and
adipose tissue), stimulates glycogen synthesis, inhibits glycogen breakdown.
 Lipid metabolism: Stimulates fat synthesis, inhibits lipolysis.
 Protein metabolism: Stimulates amino acid uptake and protein synthesis.
 Growth factor–like role: Promotes cell growth and differentiation.
Control
 Major regulator: Blood glucose levels (↑ glucose → ↑ insulin).
 Stimulated by: amino acids, fatty acids, incretins (GLP-1, GIP), parasympathetic
activity.
 Inhibited by: sympathetic activity (noradrenaline), somatostatin, low glucose.
Feedback
 Negative feedback: As blood glucose decreases, insulin secretion falls.
Other Regulatory Factors
 Exercise and fasting reduce insulin secretion.
 Obesity, type 2 diabetes → insulin resistance.
 Therapeutic insulin is used in diabetes mellitus.
2. Glucagon
Definition
A peptide hormone that raises blood glucose by stimulating glycogen breakdown and
gluconeogenesis.
Origin
 Secreted by α-cells of the pancreatic islets of Langerhans.
Structure
 Single-chain polypeptide, 29 amino acids long.
General Function
 Carbohydrate metabolism: Stimulates glycogenolysis and gluconeogenesis in the
liver → ↑ blood glucose.
 Lipid metabolism: Stimulates lipolysis and ketone production.
 Protein metabolism: Enhances amino acid uptake in the liver for gluconeogenesis.
Control
 Major regulator: Low blood glucose (hypoglycemia → ↑ glucagon).
 Stimulated by: amino acids (especially alanine, arginine), sympathetic activity
(epinephrine).
 Inhibited by: insulin, somatostatin, high blood glucose, fatty acids.
Feedback
 Negative feedback: As blood glucose rises, glucagon secretion decreases.
Other Regulatory Factors
 Stress and exercise increase glucagon secretion.
  In diabetes mellitus, inappropriate glucagon secretion contributes to hyperglycemia.
3. Somatostatin (Pancreatic Somatostatin)
Definition
An inhibitory peptide hormone that regulates insulin and glucagon secretion, as well as
gastrointestinal hormones.
Origin
 Secreted by δ-cells of the pancreatic islets of Langerhans.
 Also produced in the hypothalamus and gastrointestinal tract.
Structure
 Exists as 14–28 amino acid peptides (pancreatic form usually 14 aa).
General Function
 Inhibits insulin and glucagon secretion.
 Inhibits gastrointestinal hormones (gastrin, secretin, cholecystokinin).
 Reduces GI motility and nutrient absorption.
 Acts as a paracrine regulator within the pancreas.
Control
 Stimulated by high blood glucose, amino acids, fatty acids, and GI hormones.
 Acts locally in pancreas to balance insulin and glucagon secretion.
Feedback
 Negative feedback on its own release (short-lived action due to short half-life).
Other Regulatory Factors
 Somatostatin analogs (e.g., octreotide) are used in medicine to treat acromegaly,
insulinomas, and GI hormone–secreting tumors.
 Plays a role in preventing extremes of blood glucose swings after meals.
In summary:
 Insulin lowers blood glucose (anabolic).
 Glucagon raises blood glucose (catabolic).
 Somatostatin modulates both, acting as a “brake” on pancreatic and gut hormones.

F), ADRENAL GLAND HORMONES

Adrenal cortex (cortisol, aldosterone, androgens); adrenal medulla (adrenaline,
noradrenaline).

1. Adrenal Cortex Hormones

The adrenal cortex has three zones, each secreting specific steroid hormones:
 Zona fasciculata → Cortisol (glucocorticoid)
 Zona glomerulosa → Aldosterone (mineralocorticoid)
 Zona reticularis → Androgens (DHEA, androstenedione)
i). Cortisol (Glucocorticoid)
Definition
A steroid hormone that regulates metabolism, stress response, and immune function.
Origin
 Secreted by zona fasciculata of adrenal cortex.
Structure
 Derived from cholesterol (lipophilic).
 Circulates bound to corticosteroid-binding globulin (CBG).
General Function
 Metabolism: Stimulates gluconeogenesis, increases blood glucose, promotes protein
catabolism, and lipolysis.
 Immune system: Anti-inflammatory and immunosuppressive.
 Cardiovascular system: Helps maintain vascular tone and blood pressure.
 Stress response: Increases energy availability during stress.
Control
  Controlled by Hypothalamic-Pituitary-Adrenal (HPA) axis:
o CRH (hypothalamus) → ACTH (pituitary) → cortisol.

 Follows a circadian rhythm: highest in early morning, lowest at midnight.

Feedback
 Negative feedback: Cortisol inhibits CRH and ACTH secretion.
Other Regulatory Factors
 Stress overrides circadian rhythm → increases cortisol.
 Chronic excess → Cushing’s syndrome; deficiency → Addison’s disease.
ii). Aldosterone (Mineralocorticoid)
Definition
A steroid hormone that regulates sodium, potassium, and water balance.
Origin
 Secreted by zona glomerulosa of adrenal cortex.
Structure
 Derived from cholesterol.
 Circulates mostly bound to albumin.
General Function
 Increases sodium reabsorption in renal distal tubules/collecting ducts.
 Increases potassium and hydrogen ion excretion.
 Maintains extracellular fluid volume and blood pressure.
Control
 Regulated mainly by the Renin-Angiotensin-Aldosterone System (RAAS):
o ↓ Blood pressure/Na⁺ → ↑ Renin → ↑ Angiotensin II → ↑ Aldosterone.

 Also stimulated by hyperkalemia (high potassium).

 Weakly influenced by ACTH.
Feedback
 Negative feedback via normalization of blood pressure, Na⁺, and K⁺.
Other Regulatory Factors
 High sodium intake suppresses aldosterone.
  Drugs: Angiotensin converting enzymes (ACE)A inhibitors and Angiotensin 11
receptor blockers (ARBs) reduce aldosterone secretion.
 Excess → Conn’s syndrome (primary hyperaldosteronism).
iii). Adrenal Androgens (Dehydroepiandrosterone) DHEA, Androstenedione)
Definition
Weak steroid hormones that serve as precursors for sex steroids.
Origin
 Secreted by zona reticularis of adrenal cortex.
Structure
 Steroid hormones derived from cholesterol.
General Function
 Contribute to secondary sexual characteristics (especially in females).
 Converted to testosterone/estrogen in peripheral tissues.
 In females: responsible for pubic and axillary hair, libido.
 In males: minimal role (testicular testosterone dominates).
Control
 Stimulated by ACTH (though less strongly than cortisol).
Feedback
 Limited negative feedback; less tightly regulated than cortisol/aldosterone.
Other Regulatory Factors
 Excess secretion → adrenal virilization in females.
 Decline with aging (adrenopause).

2. Adrenal Medulla Hormones

The adrenal medulla acts as a modified sympathetic ganglion.
1. Adrenaline (Epinephrine)
Definition
A catecholamine hormone that prepares the body for “fight or flight” response.
Origin
 Secreted by chromaffin cells of adrenal medulla.
  Derived from tyrosine.
Structure
 Catecholamine (amine hormone).
General Function
 Metabolism: Increases glycogenolysis, gluconeogenesis → raises blood glucose.
 Cardiovascular system: Increases heart rate, cardiac output, and blood pressure.
 Respiratory system: Causes bronchodilation.
 Energy mobilization: Increases lipolysis.
Control
 Direct stimulation by sympathetic nervous system (preganglionic cholinergic
fibers).
 Stress, hypoglycemia, exercise, trauma stimulate release.
Feedback
 Short-acting; terminated by reuptake, metabolism (COMT, MAO).
 No classical endocrine negative feedback loop.
Other Regulatory Factors
 β-blockers and α-blockers modulate adrenaline effects clinically.
 Overproduction (pheochromocytoma) → hypertension, palpitations, sweating.
2. Noradrenaline (Norepinephrine)
Definition
A catecholamine functioning both as a hormone and neurotransmitter, involved in vascular
tone and stress response.
Origin
 Secreted by adrenal medulla (chromaffin cells) and sympathetic nerve endings.
 Derived from tyrosine.
Structure
 Catecholamine (amine hormone).
General Function
 Cardiovascular system: Causes vasoconstriction → raises blood pressure.
 Metabolism: Mobilizes glucose and fats (less potent than adrenaline).
  Neurotransmitter role: Main transmitter of sympathetic nervous system.
Control
 Regulated by sympathetic nerve activity.
 Stress and hypotension increase release.
Feedback
 No classical negative feedback loop; inactivated by reuptake and enzymatic
breakdown (COMT, MAO).
Other Regulatory Factors
 Noradrenaline has stronger vasoconstrictive effects compared to adrenaline.
 Excess secretion (pheochromocytoma) leads to paroxysmal hypertension.
✅ Summary Table:

Region Hormone Main Function Regulation

Cortex (Zona Cortisol Metabolism, stress, HPA axis (ACTH)

fasciculata) immunity

Cortex (Zona Aldosterone Na⁺/K⁺ balance, BP RAAS, K⁺ levels

glomerulosa) control

Cortex (Zona Androgens Secondary sex traits ACTH

reticularis)

Medulla Adrenaline Fight-or-flight, ↑ HR, ↑ Sympathetic

glucose stimulation

Medulla Noradrenaline Vasoconstriction, ↑ BP Sympathetic

stimulation

G). GONADAL HORMONES

Gonadal hormones are sex hormones produced by the gonads (testes in males and
ovaries in females).
They are mainly steroids derived from cholesterol and are responsible for reproduction,
sexual development, and secondary sexual characteristics.’
1. MALE GONADAL HORMONES (TESTES)
a) Testosterone (main androgen)
Testosterone is the main male sex hormone (androgen), which is a steroid hormone
derived from cholesterol, and synthesized mainly in the Leydig cells of the testes (small
amounts also in ovaries and adrenal cortex)
Regulation
Controlled by the Hypothalamic–Pituitary–Gonadal (HPG) axis:
o GnRH (from hypothalamus) → stimulates anterior pituitary.

o LH (from anterior pituitary) → stimulates Leydig cells → testosterone

production.
o Negative feedback: Testosterone inhibits GnRH & LH secretion to maintain
balance.
Transport
In blood, testosterone is mostly bound:
o Sex Hormone–Binding Globulin (SHBG): ~60%.

o Albumin (weak binding): ~38%.

o Free testosterone (active form): ~2%.

Functions
a) Developmental
 Differentiation of male reproductive system in fetus.
 Descent of testes during development.
b) Pubertal
 Growth of penis, scrotum, prostate, and seminal vesicles.
 Secondary sexual characteristics:
o Deepening of voice (larynx growth).

o Facial, axillary, pubic hair.

o Increased muscle mass and bone density.

o Male pattern fat distribution.

c) Reproductive
 Stimulates spermatogenesis (with FSH support).
 Maintains libido and sexual function.
d) Metabolic
  Increases protein synthesis (anabolic effect → muscle growth).
 Stimulates red blood cell production (erythropoiesis).
 Influences fat metabolism.
Conversion
 Converted to Dihydrotestosterone (DHT) in some tissues (via 5α-reductase) → more
potent, critical for prostate growth & external genitalia.
 Converted to Estradiol (via aromatase) in fat & brain → helps in bone health and
mood regulation.
Clinical Aspects
 Low testosterone (Hypogonadism):
o In children: Delayed puberty, underdeveloped genitalia.

o In adults: Low libido, infertility, muscle wasting, osteoporosis.

 High testosterone (Excess):

o Precocious puberty in boys.

o Aggression, acne, increased risk of prostate enlargement.

 Medical use: Testosterone replacement therapy (TRT), anabolic steroids (misused in

sports).

It shows:
 Hypothalamus (GnRH) → stimulates
  Anterior Pituitary (LH, FSH) → stimulates
 Testes (Leydig cells) → produce
 Testosterone → which then drives spermatogenesis, male characteristics, muscle
growth, and libido.
Negative feedback is shown where testosterone regulates hypothalamus & pituitary to keep
balance.
Summary Statement:
Testosterone is the primary male androgen responsible for male reproductive development,
secondary sexual characteristics, spermatogenesis, anabolic effects, and libido. It is tightly
regulated by the hypothalamic-pituitary-gonadal axis (HPG axis) and acts directly or via
conversion to Dihydrotestosterone (DHT) and estradiol.

b). OTHER ANDROGENS

1. Dihydrotestosterone (DHT)
 Formed by conversion of testosterone via 5α-reductase enzyme.
 More potent than testosterone (binds androgen receptors more strongly).
 Main actions:
o Development of external male genitalia (penis, scrotum, prostate) in fetus.

o Male-pattern hair growth (beard, body hair, baldness).

o Prostate growth.

 Clinical relevance:
o Excess → benign prostatic hyperplasia (BPH), prostate cancer.

o Deficiency → ambiguous genitalia in male infants.

o Drugs blocking 5α-reductase (e.g., finasteride) are used in BPH & baldness.

2. Dehydroepiandrosterone (DHEA)
 Produced mainly by the adrenal cortex (zona reticularis).
 Weak androgen on its own, but can be converted to testosterone & estrogen in
peripheral tissues.
 Important in adrenarche (early puberty).
 Levels decline with age.
3. Androstenedione
  Precursor of testosterone and estrone.
 Secreted by both adrenal glands and gonads.
 Weak androgen activity, but an important intermediate in sex hormone biosynthesis.
4. Androstenediol
 Produced from dehydroepiandrosterone (DHEA) and androstenedione.
 Weak androgen with some estrogenic activity.
 Helps regulate pubertal changes.
5. 11-Ketotestosterone
 Produced from adrenal precursors.
 Important androgen in some conditions (especially congenital adrenal hyperplasia).
Summary Table

Androgen Source Potency Key Role

Testosterone Testes (Leydig Strong Male development,

cells) spermatogenesis, libido

DHT Peripheral Very External genitalia,

tissues (from T) strong prostate, hair patterns

DHEA Adrenal cortex Weak Pubertal development,

precursor

Androstenedione Adrenal & Weak Precursor for

gonads testosterone/estrogen

Androstenediol Adrenal/gonads Weak Puberty, minor

androgen

11- Adrenal Moderate Active androgen in

Ketotestosterone adrenal disorders

In summary:
Androgen Synthesis Pathway Diagram
 Cholesterol → Pregnenolone → DHEA → Androstenedione → Testosterone
 Testosterone can be further converted into:
o DHT (by 5α-reductase, more potent androgen)

o Estradiol (by aromatase, estrogen pathway)

 🔹 Adrenal glands mainly supply DHEA & androstenedione (weak androgens).
🔹 Testes produce testosterone (the main active androgen).

Testosterone is the main androgen, but other androgens like DHT, DHEA, and
androstenedione play supportive or precursor roles, with DHT being the most biologically
potent
2). FEMALE GONADAL HORMONES (OVARIES)
a) Estrogens (estradiol, estrone, estriol)
1. Definition
 Estrogens are the primary female sex hormones.
 They are steroid hormones synthesized mainly in the ovaries (granulosa cells),
placenta (during pregnancy), and to a smaller extent in the adrenal glands and testes.
 The three main naturally occurring estrogens in humans are:
1. Estradiol (E2) – the most potent and predominant.
2. Estrone (E1) – weaker, dominant after menopause.
3. Estriol (E3) – weakest, mainly produced during pregnancy.
2. Types of Estrogens
a) Estradiol (E2)
 Most abundant in reproductive-age women.
 Produced by granulosa cells in the ovary (from androgens via aromatase enzyme).
 Functions:
o Stimulates growth of endometrium (proliferative phase).

o Development of secondary sexual characteristics (breasts, hips, fat

distribution).
o Maintains bone density and cardiovascular health.

b) Estrone (E1)
 Formed from androstenedione (mainly in adipose tissue).
 Dominant estrogen after menopause.
 Weaker effect than estradiol.
c) Estriol (E3)
 Produced in large amounts by the placenta during pregnancy (from fetal adrenal
DHEA).
  Weakest estrogen.
 Important for maintaining pregnancy and preparing the body for childbirth.
3. Regulation
 Hypothalamus (GnRH) → stimulates anterior pituitary.
 FSH & LH → act on ovaries.
 Ovarian follicles → produce estrogens.
 Negative feedback: High estrogen suppresses FSH/LH, but mid-cycle estradiol surge
stimulates LH surge, leading to ovulation.
4. Transport
 Bound to Sex Hormone–Binding Globulin (SHBG) and albumin.
 Small fraction remains free (biologically active).
5. Functions of Estrogens
 Reproductive system:
o Growth of uterus, vagina, and fallopian tubes.

o Regulates menstrual cycle (proliferative phase).

o Prepares endometrium for progesterone action.

 Secondary sexual characteristics: Breast development, fat distribution (hips, thighs,

buttocks).
 Bone & metabolism:
o Maintains bone density (inhibits osteoclast activity).

o Improves lipid profile (↑ HDL, ↓ LDL).

 Cardiovascular system: Vasodilation, protects against atherosclerosis.

 Pregnancy (especially estriol): Uterine growth, increased blood flow, breast
development.
6. Clinical Aspects
 Deficiency (low estrogens):
o Delayed puberty, amenorrhea, osteoporosis, infertility, menopausal symptoms
(hot flashes).
 Excess (high estrogens):
o Gynecomastia in males, precocious puberty in females, risk of
endometrial/breast cancer.
  Medical uses:
o Contraceptives, hormone replacement therapy (HRT), infertility treatments.

Summary Table

Estrogen Source Potency Key Role

Estradiol Ovaries (granulosa cells) Strongest Menstrual cycle, female traits,

(E2) fertility

Estrone (E1) Adipose tissue (post- Moderate Post-menopausal estrogen

menopause)

Estriol (E3) Placenta (pregnancy) Weakest Maintains pregnancy

b) Progesterone
Definition
 Progesterone is a steroid hormone primarily secreted by the corpus luteum in the
ovary after ovulation.
 During pregnancy, it is also produced by the placenta (major source after 12 weeks).
 Smaller amounts are secreted by the adrenal cortex and testes.
2. Regulation
 Controlled by the Hypothalamic–Pituitary–Gonadal (HPG) axis:
o GnRH (hypothalamus) → stimulates anterior pituitary.

o LH → stimulates corpus luteum → progesterone production.

 Levels rise during the luteal phase of the menstrual cycle and during pregnancy.
3. Transport
 Circulates bound to albumin and corticosteroid-binding globulin (CBG).
 Only a small fraction is free and biologically active.
4. Functions
a) Reproductive System
 Prepares endometrium for implantation (secretory phase).
 Maintains early pregnancy by supporting uterine lining.
 Inhibits uterine contractions (prevents premature labor).
 Thickens cervical mucus (forms a barrier to sperm during luteal phase).
b) Pregnancy
 Produced by placenta → maintains uterine quiescence.
 Stimulates growth of mammary glands (with estrogen) in preparation for lactation.
c) Other Roles
 Thermogenic effect: Slight increase in basal body temperature after ovulation (used in
fertility tracking).
 Modulates immune system to prevent maternal rejection of fetus.
 Has mild natriuretic effect (opposes aldosterone at kidney level).
5. Clinical Aspects
 Low progesterone:
o Infertility (failure of implantation).

o Recurrent miscarriages.

o Irregular or absent menstrual cycles.

 Excess progesterone:
o Bloating, fatigue, breast tenderness.

 Medical uses:
o Part of oral contraceptives (combined with estrogen).

o Hormone replacement therapy (HRT).

o Treatment of menstrual disorders and prevention of preterm labor.

6. Progesterone vs Estrogen (Quick Comparison)

Feature Estrogen Progesterone

Main phase Follicular (first half) Luteal (second half)

Endometrium Proliferation (growth) Secretory changes (implantation

effect ready)

Cervical mucus Thin, watery (sperm Thick, sticky (sperm barrier)

penetration)

Pregnancy role Uterine growth Maintains pregnancy, prevents

contractions

Bone & heart Protects bone, improves Mild, secondary role

lipids
 Summary:
Progesterone is the hormone of pregnancy, preparing and maintaining the endometrium,
preventing uterine contractions, and supporting fetal survival. It works hand-in-hand with
estrogen but dominates in the luteal phase and pregnancy.
c) Inhibin
Definition
Inhibin is a peptide hormone secreted mainly by the gonads (testes and ovaries).
Its main role is to inhibit Follicle-Stimulating Hormone (FSH) secretion from the
anterior pituitary.
Works as part of the negative feedback mechanism in the Hypothalamic–Pituitary–
Gonadal (HPG) axis.
2. Types
Inhibin A
Produced mainly by the corpus luteum in females (after ovulation).
Levels are highest in the luteal phase of the menstrual cycle.
Inhibin B
Produced by granulosa cells in ovaries (follicular phase) and Sertoli cells in testes.
In males, levels correlate with spermatogenesis activity.
3. Sources
Females: Granulosa cells of ovarian follicles, corpus luteum, and placenta (during
pregnancy).
Males: Sertoli cells of seminiferous tubules.
4. Regulation
Stimulated by:
FSH → increases inhibin production.
Negative feedback:
Inhibin inhibits FSH secretion (but does not directly affect LH).
5. Functions
In Females:
Regulates menstrual cycle by inhibiting FSH.
Controls the number of developing follicles → ensures normally only one dominant
follicle matures for ovulation.
 In pregnancy, placenta secretes inhibin A to help regulate hormone balance.
In Males:
Secreted by Sertoli cells in proportion to sperm production.
Inhibits FSH release → regulates spermatogenesis.
Used clinically as a marker of Sertoli cell function and sperm production.
6. Clinical Aspects
Low inhibin in women: May indicate reduced ovarian reserve or approaching
menopause.
High inhibin A (in pregnancy): Used in prenatal screening (e.g., combined with hCG,
AFP, estriol for Down syndrome screening).
Low inhibin B in men: Suggests impaired spermatogenesis or Sertoli cell dysfunction
(infertility marker).
Summary Statement:
Inhibin is a gonadal peptide hormone (Inhibin A & B) that negatively regulates FSH.
In females → controls follicle development.
In males → regulates spermatogenesis.

3. Regulation of Gonadal Hormones

1. Overview
The production of gonadal hormones (testosterone, estrogen, progesterone, inhibin) is
controlled by the Hypothalamic–Pituitary–Gonadal (HPG) Axis, which uses feedback
mechanisms to maintain balance.
2. Stepwise Regulation
a) Hypothalamus
 Secretes GnRH (Gonadotropin-Releasing Hormone) in a pulsatile manner.
 Stimulates the anterior pituitary to release FSH and LH.
 Frequency and amplitude of GnRH pulses determine whether FSH or LH dominates.
b) Anterior Pituitary
 LH (Luteinizing Hormone):
o Males → stimulates Leydig cells to produce testosterone.
 o Females → stimulates theca cells to produce androgens (precursors for
estrogen).
o Also triggers ovulation and formation of corpus luteum.

 FSH (Follicle-Stimulating Hormone):

o Males → acts on Sertoli cells, supporting spermatogenesis & stimulating
inhibin B release.
o Females → stimulates granulosa cells for follicle development & estrogen
synthesis (via aromatase).
c) Gonads
 Testes (Males): Produce testosterone (and small amounts of estrogen, inhibin B).
 Ovaries (Females): Produce estrogen, progesterone, and inhibin A/B depending on
cycle phase.
d) Feedback Control
 Negative Feedback:
o Testosterone (in men), estrogen & progesterone (in women) inhibit
hypothalamus (GnRH) and pituitary (LH/FSH).
o Inhibin (A & B): selectively inhibits FSH secretion.

 Positive Feedback (special case in females):

o Mid-cycle estradiol surge → stimulates LH surge → causes ovulation.

3. Summary of Regulation

Level Hormones Effect

Released

Hypothalamus GnRH Stimulates anterior

pituitary

Anterior LH, FSH Stimulate gonads

Pituitary

Gonads (Male) Testosterone, Spermatogenesis,

Inhibin B negative feedback

Gonads Estrogen, Menstrual cycle

(Female) Progesterone, regulation,
Inhibin A/B feedback

Feedback Testosterone, Control GnRH,

Estrogen, FSH, LH release
 Progesterone,
Inhibin

Clinical Relevance
 Disruption in regulation → infertility, menstrual irregularities, low libido,
hypogonadism.
 Drugs targeting regulation:
o GnRH agonists/antagonists – used in fertility treatments, prostate cancer,
endometriosis.
o FSH/LH analogs – used in assisted reproduction.

o Testosterone/Estrogen replacement – in hypogonadism or menopause.

In summary:
The HPG axis tightly regulates gonadal hormones through a balance of stimulation (GnRH
→ FSH/LH) and feedback inhibition (testosterone, estrogen, progesterone, inhibin).

CLINICAL ASPECTS OF GONADAL HORMONES

1. Male Gonadal Hormones (Androgens – Testosterone, DHT)
 Deficiency (Hypogonadism):
o Delayed puberty, infertility, erectile dysfunction, muscle wasting,
osteoporosis, low libido.
 Excess:
o Precocious puberty, acne, aggression, prostate enlargement, androgenic
alopecia (baldness).
 Clinical uses:
o Testosterone replacement therapy (TRT).

o Anabolic steroids (abused in sports).

o 5α-reductase inhibitors (e.g., finasteride) for BPH and baldness.

2. Female Gonadal Hormones

a) Estrogens (Estradiol, Estrone, Estriol)
 Deficiency:
o Primary/secondary amenorrhea, infertility, osteoporosis, hot flashes
(menopause).
 Excess:
 o Endometrial hyperplasia/cancer, breast cancer risk, precocious puberty,
gynecomastia in males.
 Clinical uses:
o Contraceptives, HRT in menopause, infertility treatment, osteoporosis
prevention.
b) Progesterone
 Deficiency:
o Recurrent miscarriages, infertility (implantation failure), irregular cycles.

 Excess:
o Bloating, mood swings, fatigue.

 Clinical uses:
o Oral contraceptives (with estrogen).

o Luteal phase support in IVF.

o Prevention of preterm labor.

c) Inhibin
 Clinical role:
o Marker of ovarian reserve (in fertility evaluation).

o Inhibin B reduced in menopause; used in fertility testing.

3. Disorders Related to Gonadal Hormones

 Polycystic Ovary Syndrome (PCOS): ↑ androgens in females → infertility,
hirsutism, irregular cycles.
 Menopause: ↓ estrogens → hot flashes, osteoporosis, cardiovascular risk.
 Andropause (male aging): Gradual ↓ testosterone → fatigue, muscle loss, low libido.
 Congenital Adrenal Hyperplasia (CAH): Excess adrenal androgens → ambiguous
genitalia, early virilization.
✅ Quick Mnemonic for Clinical Aspects:

 “D-E-U-S” → Deficiency, Excess, Uses, Syndromes

✅ Summary:

 Testes: Produce testosterone → male sexual development, spermatogenesis.

  Ovaries: Produce estrogen & progesterone → female sexual development, menstrual
cycle, pregnancy.
 Both sexes produce inhibin (regulates FSH).

H). PLACENTAL HORMONES

The placenta acts as a temporary endocrine organ during pregnancy, producing several
hormones essential for maintaining pregnancy, fetal growth, and preparing the mother’s body
for childbirth and lactation. Two key hormones are human chorionic gonadotropin (hCG) and
human placental lactogen (hPL).
1. Protein/Peptide Hormones
The three key protein/peptide hormones produced by the placenta are Human Chorionic
Gonadotropin (hCG), Human Placental Lactogen (hPL), and Relaxin, which are vital for
maintaining pregnancy by supporting the corpus luteum, promoting fetal growth, and
preparing the mother's body for childbirth, respectively.
a). Human Chorionic Gonadotropin (hCG)
1. Definition
 hCG is a glycoprotein hormone produced mainly by the syncytiotrophoblast cells
of the placenta during pregnancy.
 Structurally similar to LH, FSH, and TSH (they share an identical α-subunit but
differ in β-subunit).
 hCG mimics LH activity and is crucial for maintaining pregnancy.
2. Structure
 Composed of α and β subunits:
o α-subunit: Common to LH, FSH, and TSH.

o β-subunit: Unique to hCG → provides hormone specificity (basis of

pregnancy tests).
3. Functions of hCG
1. Maintains Corpus Luteum
o Stimulates the corpus luteum to continue producing progesterone & estrogen
in early pregnancy.
o Prevents menstruation and supports the endometrium for implantation.

2. Supports Fetal Development

 o Promotes differentiation of fetal testes → stimulates Leydig cells to produce
testosterone, essential for male genitalia development.
3. Placental Development
o Modulates immune tolerance to prevent maternal rejection of the fetus.

4. Marker for Pregnancy

o Detectable in maternal blood and urine within 6–10 days after fertilization.

o Basis of most pregnancy tests.

4. Clinical Uses
 Diagnostic:
o Pregnancy test (blood or urine – detects β-hCG).

o Ectopic pregnancy or threatened abortion (abnormal hCG rise).

o Gestational trophoblastic disease (e.g., hydatidiform mole, choriocarcinoma

→ very high hCG).
o Tumor marker (testicular cancers, certain ovarian cancers).

 Therapeutic:
o Used in infertility treatment to induce ovulation (in women) or testosterone
production (in men).
5. Clinical Relevance
 High hCG levels:
o Multiple pregnancies (twins, triplets).

o Hydatidiform mole, choriocarcinoma.

o Certain cancers (testicular, ovarian, hepatocellular carcinoma).

 Low hCG levels:

o Ectopic pregnancy.

o Threatened or missed abortion.

Summary Statement:
hCG is a placental hormone that maintains pregnancy by supporting the corpus luteum and
progesterone secretion. It is the earliest and most reliable marker of pregnancy, with
additional roles in fetal development and as a tumor marker.
2. Human Placental Lactogen (hPL), also called Human Chorionic
Somatomammotropin)
Definition
A polypeptide hormone with structural similarity to growth hormone and prolactin, involved
in maternal metabolic adaptation and fetal growth.
Origin
 Produced by syncytiotrophoblast cells of the placenta, secreted from ~6 weeks of
pregnancy, increasing progressively until term.
Structure
 Single-chain polypeptide hormone, ~191 amino acids.

 A protein hormone, structurally similar to growth hormone (GH) and prolactin.

 Half-life: Short (≈ 20 minutes).
 Secreted directly into maternal blood (not into fetal circulation).

General Function
 Maternal metabolism adaptation:
o Induces insulin resistance in the mother → ensures adequate glucose supply
to the fetus.
o Promotes lipolysis → increases maternal free fatty acids (energy source for
mother, sparing glucose for fetus).
 Fetal growth: Provides continuous nutrient supply.
 Breast development: Has prolactin-like activity, preparing mammary glands for
lactation.
Control
 Secretion increases steadily throughout pregnancy, reaching highest levels at term.
 Directly proportional to placental size and function.
Feedback
 No classic feedback loop; levels depend on placental growth.
Other Regulatory Factors
 hPL levels are used as an indicator of placental function.
 Low hPL → intrauterine growth restriction (IUGR) or placental insufficiency.
 High hPL → multiple pregnancies or gestational diabetes.
Clinical Significance
 Normal Pregnancy: High maternal serum hPL indicates good placental function.
  Low Levels: May suggest placental insufficiency, risk of intrauterine growth
restriction (IUGR).
 Excessive Levels: Seen in multiple pregnancies (twins, triplets) due to larger
placental mass.
 Role in Gestational Diabetes:
o hPL is one of the key hormones causing maternal insulin resistance in
pregnancy → can unmask diabetes in predisposed women.
3. Relaxin.
1. Source
 Secreted by:
o Corpus luteum (early pregnancy).

o Placenta & decidua (later pregnancy).

o Also found in ovaries, uterus, heart, and kidneys (small amounts).

2. Structure
 A polypeptide hormone (similar in structure to insulin).
3. Functions
a) During Pregnancy
 Cervical softening → prepares cervix for dilation at labor.
 Pelvic ligament relaxation → increases pelvic flexibility, widens birth canal.
 Uterine relaxation (early pregnancy) → helps prevent premature contractions.
 Increases blood flow → by vasodilation of renal and systemic blood vessels.
b) Non-pregnant Women
 Produced during the luteal phase of the menstrual cycle.
 Helps prepare the endometrium for possible implantation.
c) Other Roles
 Renal system: Increases renal blood flow and glomerular filtration rate (GFR).
 Cardiovascular system: Vasodilatory effect helps in adapting maternal circulation to
pregnancy.
 Connective tissue: Modulates collagen metabolism → increased elasticity.
4. Clinical Aspects
  High Relaxin Levels: Associated with multiple pregnancies and higher risk of pelvic
girdle pain.
 Low Levels: May be linked to preterm labor risk or difficulty in cervical ripening.
 Therapeutic Interest: Studied for potential use in treating heart failure and fibrotic
diseases (because of vasodilation and anti-fibrotic properties).
✅ In short: Relaxin is the “pregnancy softening hormone” — it softens the cervix, relaxes
ligaments, and improves blood flow to support pregnancy and childbirth.
2. Steroid Placental Hormones
a) Progesterone
Source
Early pregnancy: Corpus luteum (stimulated by hCG).
After ~12 weeks: Placenta takes over.
Functions
 Maintains the decidua (endometrium) for implantation.
 Keeps the uterus in a quiescent (relaxed) state by inhibiting contractions.
 Stimulates development of breast alveoli (with estrogen).
 Modulates maternal immune tolerance to prevent fetal rejection.
Clinical Aspects
Deficiency: Risk of miscarriage, preterm labor.
Therapeutic uses: Luteal phase support in IVF, prevention of preterm labor, contraception.
Stimulates breast alveolar development (with estrogen).
b) Estrogens (mainly Estriol, also Estradiol & Estrone)
Source
 Placenta itself cannot make estrogens directly → depends on fetal adrenal DHEA-S
(dehydroepiandrosterone sulfate) as a precursor.
 Estriol (E3) is the dominant estrogen of pregnancy.
Functions
 Promotes uterine growth and increased blood flow.
 Prepares myometrium for labor (↑ oxytocin receptors, gap junctions).
 Stimulates breast ductal system growth for lactation.
 Increases liver production of binding proteins (e.g., SHBG).
Clinical Aspects
  Low estriol levels: May indicate fetal distress, anencephaly, or placental
insufficiency.
 High levels: Seen in multiple pregnancies.
 Therapeutic uses: Estrogen therapy in contraception, HRT.
3. Other Hormones & Factors
 Corticotropin-Releasing Hormone (CRH): Produced by placenta, helps regulate
timing of labor.
 Placental Growth Hormone (PGH): Regulates maternal insulin resistance and fetal
growth.
 Prostaglandins: Involved in labor induction.
✅ Summary Table of Placental Hormones

Hormone Type Source Function

hCG Glycoprotein Syncytiotrophoblast Maintains corpus luteum,

pregnancy tests

hPL Peptide Syncytiotrophoblast Alters maternal

metabolism, prepares breast

Relaxin Peptide Placenta & corpus Cervix softening, ligament

luteum relaxation

Progesterone Steroid Placenta (after wk 12) Maintains pregnancy,

inhibits contractions

Estrogens (esp. Steroid Placenta (from fetal Uterine growth, breast prep
Estriol) DHEA)

CRH & PGH Peptides Placenta Labor timing, fetal growth

regulation

✅ In short: The placenta is not just for nutrient exchange — it also works as an endocrine
gland ensuring pregnancy maintenance, fetal growth, and preparation for birth and lactation.

Other Tissue Hormones

1. Kidney – Erythropoietin (EPO)
Definition
A glycoprotein hormone that stimulates red blood cell production in the bone marrow.
Origin
 Produced mainly by peritubular interstitial fibroblasts in the renal cortex.
 Small amounts also produced by the liver (especially in the fetus).
Structure
 Glycoprotein, ~165 amino acids.
General Function
 Promotes erythropoiesis: increases proliferation and differentiation of erythroid
progenitor cells in bone marrow.
 Enhances oxygen-carrying capacity of blood.
Control
 Regulated by tissue oxygen tension:
o Hypoxia → ↑ EPO synthesis.

o Normoxia → ↓ EPO synthesis.

 Mediated by hypoxia-inducible factor (HIF-1α).

Feedback
 Rising red cell mass (↑ O₂ delivery) → ↓ EPO production.
Other Regulatory Factors
 Increased in chronic hypoxia (high altitude, lung disease).
 Decreased in chronic kidney disease → anemia (treated with recombinant EPO).
2. Stomach – Gastrin
Definition
A peptide hormone that stimulates gastric acid secretion and promotes gastric motility.
Origin
 Secreted by G cells in the antrum of the stomach and duodenum.
Structure
 Peptide hormone; active forms include G17 (little gastrin) and G34 (big gastrin).
General Function
 Stimulates parietal cells → ↑ HCl secretion.
 Stimulates chief cells → ↑ pepsinogen secretion.
  Promotes gastric mucosal growth and motility.
Control
 Stimulated by:
o Presence of peptides/amino acids in stomach.

o Gastric distension.

o Vagus nerve (via gastrin-releasing peptide).

 Inhibited by:
o Low stomach pH (<3).

o Somatostatin.

Feedback
 Acid (HCl) in stomach provides negative feedback → inhibits further gastrin release.
Other Regulatory Factors
 Excess secretion → Zollinger-Ellison syndrome (gastrinoma → severe peptic ulcers).
 Antacids and proton pump inhibitors may increase gastrin due to reduced acidity.
3. Heart – Atrial Natriuretic Peptide (ANP)
Definition
A peptide hormone that promotes sodium and water excretion to reduce blood volume and
pressure.
Origin
 Secreted by atrial myocytes in response to atrial stretch (↑ blood volume).
Structure
 28-amino acid peptide.
General Function
 Increases renal excretion of sodium (natriuresis) and water (diuresis).
 Dilates blood vessels (vasodilation).
 Inhibits renin, aldosterone, and ADH secretion.
 Overall effect: ↓ blood pressure and volume.
Control
 Stimulated by atrial stretch due to increased blood volume or pressure.
Feedback
 Reduced blood volume and atrial stretch → ↓ ANP secretion.
Other Regulatory Factors
 Counteracts renin-angiotensin-aldosterone system (RAAS).
 Elevated ANP levels in heart failure (marker of severity, BNP more commonly
measured).
4. Adipose Tissue – Leptin
Definition
A protein hormone that regulates appetite, energy balance, and metabolism.
Origin
 Secreted mainly by white adipose tissue (adipocytes).
Structure
 167-amino acid peptide hormone.
General Function
 Acts on hypothalamus to suppress appetite (anorexigenic effect).
 Increases energy expenditure.
 Signals the brain about body fat stores ("satiety hormone").
 Plays a role in reproduction, immune regulation, and bone metabolism.
Control
 Circulating leptin levels are proportional to fat mass.
 Increased by feeding, decreased by fasting.
Feedback
 Acts in negative feedback loop with hypothalamus to regulate food intake and body
weight.
Other Regulatory Factors
 Leptin resistance occurs in obesity (high leptin but brain unresponsive).
 Deficiency (rare genetic mutation) → severe obesity, hyperphagia, infertility.
 Interacts with insulin and ghrelin in appetite regulation.
✅ Summary Table: Hormones from Other Tissues

Tissue Hormone Main Function Control

Kidney Erythropoietin ↑ RBC production Hypoxia (HIF pathway)

Stomac Gastrin ↑ Gastric acid, motility Amino acids, vagus nerve,

h inhibited by low pH

Heart ANP Natriuresis, diuresis, ↓ BP Atrial stretch (↑ volume)

Adipose Leptin Suppresses appetite, Fat mass, feeding/fasting

regulates fat stores