Graciela Jahn
National Scientific and Technical Research Council, Imbecu Conicet, Department Member
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The effect of stress in wild vertebrates has been little investigated, especially in crocodilians. In the wild, crocodilians face numerous stressors such as climatic factors, toxicant exposure, and infection. Exposure to stressors may... more
The effect of stress in wild vertebrates has been little investigated, especially in crocodilians. In the wild, crocodilians face numerous stressors such as climatic factors, toxicant exposure, and infection. Exposure to stressors may affect the physiological processes of crocodilians, with consequences on its fitness and survival. We experimentally investigated the effect of a 4‐week exposure to environmental challenges (food restriction, water restriction and high temperature) on growth, immunological investment and corticosterone levels of juvenile Caiman latirostris. White blood cells counts, natural antibody (NAb) levels and complement system activity were evaluated to characterize the influence of those treatments on the immune system. We found deprivation of food resulted in reduction in growth and body condition, whereas high temperature had a beneficial effect on the variables measured. Individuals exposed to heat treatment (37 ± 1°C) grew more, and obtained better body con...
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In brief The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Thyroid dysfunctions lead... more
In brief The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal–fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.
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In the wild, vertebrates face numerous unpredictable and harmful stressors such as storms, fires, earthquakes, tsunamis, and others. A typical physiological response to a perceived stressor is the increased secretion of glucocorticoids.... more
In the wild, vertebrates face numerous unpredictable and harmful stressors such as storms, fires, earthquakes, tsunamis, and others. A typical physiological response to a perceived stressor is the increased secretion of glucocorticoids. Such a response is adaptive in the short term and could modulate the cellular immune response. Our purpose in this study was to examine the effect of stimulation with adrenocorticotropin (ACTH) injection and physical restraint (PR) on plasma corticosterone (CORT) levels, and total and differential white blood cell counts in the Broad-snouted Caiman ( Caiman latirostris (Daudin, 1802)). Individuals under PR increased CORT levels over time. Otherwise, no differences were observed in the CORT concentration between individuals injected with ACTH and those injected with saline solution. High CORT concentrations in the PR caimans produced a biphasic profile on total white blood cell counts, as well as the lymphocyte and heterophil counts. This response to PR may represent a stress response with an increase in immune surveillance in organs.
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... Comportamiento territorial y fidelidad al hábitat en una población de roedores del centro de la provincia de Mendoza. Ecología Argentina 5: 17-29. CUTRERA RA, YUNES RMF & CASTRO-VAZQUEZ A. 1988. ... Nebraska Symposium on... more
... Comportamiento territorial y fidelidad al hábitat en una población de roedores del centro de la provincia de Mendoza. Ecología Argentina 5: 17-29. CUTRERA RA, YUNES RMF & CASTRO-VAZQUEZ A. 1988. ... Nebraska Symposium on Motivation 35: 1-50. DUDLEY D. 1974. ...
Research Interests: Zoology, Biology, Social Structure, Weaning, Litter, and 4 moreSigmodontinae, Home Range, Three Dimensional, and Muridae
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The expression of two forms of PRL receptor messenger RNA was measured at different stages of pregnancy and lactation in mammary gland and liver from Sprague-Dawley rats, using 32P-labeled complementary DNA probes encoding the... more
The expression of two forms of PRL receptor messenger RNA was measured at different stages of pregnancy and lactation in mammary gland and liver from Sprague-Dawley rats, using 32P-labeled complementary DNA probes encoding the extracellular part of the receptor (E probe), common to the two forms and a probe encoding the intracellular part of the long form of the receptor (I probe), that only recognizes sequences specific to the long form of the receptor. Hybridizations were performed in Northern blots obtained from electrophoreses of poly (A+) enriched RNA preparations from mammary glands and livers of rats on days 0, 6, 12, 19, and 21 of pregnancy and 5, 10, 15, and 20 of lactation. The Northern blots were also hybridized with a chicken beta-actin probe, to correct for the amount of mRNA added and the different metabolic states of the tissues. Both tissues expressed the same forms of PRL receptor mRNAs, namely bands at 2.5, 3, and 5.5 kilobases encoding the long form of the receptor and a major band at 1.8 kilobases encoding the short form. The liver expressed all the receptor mRNA forms in much higher quantity than the mammary gland, independent of the reproductive state. In liver there was an increase of all the transcripts on day 19 of pregnancy, followed by an abrupt decline at the onset of lactation, to levels lower than those of virgin rats. In contrast, mammary gland PRL receptor mRNAs were low in virgin and pregnant animals, increased significantly at day 21 of pregnancy, and continued to increase throughout lactation. Treatment of day 19 pregnant rats with the antiprogesterone RU 486 induced, 24 h later, PRL receptor mRNAs in mammary gland but not in liver. There were no significant differences in the relative proportions of long to short forms of PRL receptor mRNAs at the different reproductive states, but the proportion of the long form was slightly greater in mammary gland than in liver. Membrane PRL receptor concentrations were also measured in the same tissues used for the mRNA study by binding to a 125I-labeled monoclonal antibody (U5), which specifically recognizes the PRL receptor at a site different from the hormone binding site. The quantity of receptor measured by U5 binding was approximately 3 times higher than that measured with 125I-labeled ovine PRL.(ABSTRACT TRUNCATED AT 400 WORDS)
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Reproductive strategies vary considerably among species, but most studies have focused on a very limited number of mammalian species. Knowledge of the reproductive cycle and behavior is essential for developing and implementing in situ... more
Reproductive strategies vary considerably among species, but most studies have focused on a very limited number of mammalian species. Knowledge of the reproductive cycle and behavior is essential for developing and implementing in situ and ex situ conservation strategies for threatened and endangered species. This study aimed at characterizing the seasonal reproductive pattern of female pichis Zaedyus pichiy, a threatened small armadillo native to arid regions of Argentina and Chile, through direct observations, histological studies, and by measuring fecal immunoreactive estrogens, progestagens and glucocorticoids in 10 wild-born, captive pichis and in free-ranging individuals. Results suggest that pichis are seasonal breeders that give birth to one yearly litter of 1-2 offspring, which do not leave the burrow until they are weaned at approximately 37 days. Ovarian follicular growth seems to occur throughout the year. Fecal progestagen, estrogen and glucocorticoid concentrations were minimal during the first half of pregnancy, increased to peak concentrations of up to 3500, 200 and 200ng/g dry feces, respectively, and decreased before parturition. Postpartum progestagen concentrations were greater in lactating females than females that aborted or did not raise their offspring (p<0.0001), which is probably related to an elevated corticosteroid synthesis that contributes to maintain lactation, given that fecal glucocorticoid concentrations were of similar pattern. Observations of a second pregnancy after late abortion or death of the newborn litter and sustained follicular growth during pregnancy and lactation suggest that female pichis can become receptive briefly after having lost their litter. Fecal estrogen and progestagen concentrations of non-pregnant, non-lactating females did not have a well-defined hormonal cyclic pattern, and corpora lutea were only observed in pregnant females.
Research Interests: Biology, Endangered Species, Medicine, Biological Sciences, Ex Situ Conservation, and 15 moreFemale, Animals, Litter, Periodicity, Arid Region, Ciencias Biológicas, Dasypodidae, Feces, Captive Wild Animals, Armadillos, Ovary, Biología Reproductiva, Glucocorticoids, postpartum period, and Medical and Health Sciences
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The present study was undertaken to assess whether chronic exposition to cadmium (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As... more
The present study was undertaken to assess whether chronic exposition to cadmium (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As compared to metal non-exposed controls, PALs exposed to cadmium showed an increase in total phospholipid contents, which was associated to an increase of the incorporation of [1-14C]-methyl choline into phosphatidylcholine and of [U-14C]-glucose into total phospholipids. The incorporation of [1-14C]-methyl choline into sphingomyelin was not changed. Incorporation of [1-14C]-acetate into total fatty acids also increased but incorporation of [1-14C]-acetate into cholesterol did not change. The activity of phospholipase D decreased both in PALs from Cd exposed rats and in PAL dispersed cells treated with Cd in the culture medium from Cd non-exposed rats. In PALS from Cd exposed rats, a decrease of serum prolactin and growth hormone concentrations was determined. The results shown that cadmium modifies the lipid contents of pituitary gland and directly or indirectly the levels of prolactin and growth hormone in serum.
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The results of these experiments demonstrate that histones from brain inhibit the replication of DNA in vitro. A similar effect is observed with polylysine or polyarginine. The reversion of inhibition by polyglutamic acid or acidic... more
The results of these experiments demonstrate that histones from brain inhibit the replication of DNA in vitro. A similar effect is observed with polylysine or polyarginine. The reversion of inhibition by polyglutamic acid or acidic proteins is completed in all cases except when the DNA is previously complexed with histones, polyarginine or polylysine. This suggest that histones masking of DNA towards the polymerases involves electrostatic forces.
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Research Interests: Endocrinology, Physiology, Biology, Lactation, Medicine, and 15 moreChemokines and chemokine receptors, Pregnancy, Population, Prolactin, Internal Medicine, Female, Animals, Male, Clinical Sciences, Ciencias Biológicas, Mammary gland, B Lymphocytes, Biología Reproductiva, Leukocytes, and Paediatrics and reproductive medicine
Changes in the activity of DNA polymerase and [3H]thymidine incorporation into the DNA of the anterior pituitary gland were studied in oestrogenized male and pregnant rats. The activities of DNA polymerases alpha and beta, extracted in... more
Changes in the activity of DNA polymerase and [3H]thymidine incorporation into the DNA of the anterior pituitary gland were studied in oestrogenized male and pregnant rats. The activities of DNA polymerases alpha and beta, extracted in Tris--HCl or in sodium phosphate buffer were characterized according to their optimum pH and sensitivity to N-ethyl-maleimide. In the Tris-soluble fraction DNA polymerase activity is almost exclusively alpha, while in the phosphate soluble fraction it is a mixture of alpha and beta. The administration of oestrogens to male rats increases [3H]thymidine incorporation and enhances the activity of DNA polymerases in the Tris-soluble fraction, while the activity of the phosphate-soluble enzyme does not change. Sulpiride administration results in a further increment of [3H]thymidine incorporation and of DNA polymerase activity in the Tris-soluble fraction. In pregnant rats sulpiride also produces an increment of DNA polymerase activity only in the Tris-soluble fraction. Thus, the activity of the Tris-soluble fraction from APG behaves as DNA polymerase alpha. This activity changes in parallel with [3H]thymidine incorporation into DNA which is an indication of cell proliferation in the gland. This is discussed with respect to a negative feedback mechanism between intracellular prolactin concentration and DNA synthesis in the APG.
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Abstract The objective of this study was to determine the effect of the length of the suckling period and the dietary energy level on the duration of postpartum anestrus in Creole goats. Twenty-eight multiparous pregnant goats (bodyweight... more
Abstract The objective of this study was to determine the effect of the length of the suckling period and the dietary energy level on the duration of postpartum anestrus in Creole goats. Twenty-eight multiparous pregnant goats (bodyweight BW 39.9 ± 6.4 kg; mean ± SEM) each bearing a single fetus were used in a 2 suckling period (30 vs. 60 d) × 2 levels of energy intake (low (L) vs. high (H)) factorial design. Kids were separated from their dams 3 d after birth and then suckled twice per day until weaned at 30 or 60 d postpartum. Dams weaned at 30 d postpartum were hand milked for the next 30 d. Goats were individually fed chopped alfalfa hay + balanced concentrates (45:55 DM basis) at 3% of BW in the last month of pregnancy and at the same level to the L goats in the postpartum period when the H goats were fed at 4% of BW. Energy balance was estimated by difference between energy intake and calculated energy requirements. Duration of postpartum anestrus was estimated by determining the occurrence of ovulation from changes in blood progesterone concentrations. There were no significant lengths of suckling x energy intake level interactions. Goats on all treatments lost weight until 45 d postpartum with more weight loss on the low than the high energy intake level (L 4.06 ± 0.43 vs. H 1.99 ± 0.64 kg; P
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Introduction: OFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain, Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone during... more
Introduction: OFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain, Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone during late pregnancy and lactation. We explored if the expression of MBH components, including various receptors (R) and proteins that regulate the dopaminergic system, is altered in mid-lactating OFA compared to SD rats, which may be associated with the abnormality. Methods: Four groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30-min suckling (S); and 2 h or 4 h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (TH), PRL-R, PRL signaling molecules (activator: STAT5b; inhibitors: SOCS1, SOCS3, CIS), opioids (PENK, PDYN), and µ- and κ-opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and TH proteins by Western blot. Results: Suckling-indu...
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The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies... more
The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the i...
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Las disfunciones tiroideas son frecuentes en mujeres en edad reproductiva y son una causa común de infertilidad, fertilidad subnormal, abortos espontáneos, problemas en el embarazo y parto prematuro. Se asocian con anovulación y ciclos... more
Las disfunciones tiroideas son frecuentes en mujeres en edad reproductiva y son una causa común de infertilidad, fertilidad subnormal, abortos espontáneos, problemas en el embarazo y parto prematuro. Se asocian con anovulación y ciclos menstruales anormales. La presencia de anticuerpos antitiroideos aumenta el riesgo de aborto, infertilidad y síndrome de ovario poliquístico (SOP). Las hormonas tiroideas (HT) pueden afectar la fertilidad indirectamente, interfiriendo con el eje hipotálamo-hipófiso-gonadal, o a nivel ovárico, ya que sus receptores (TR) están presentes en la mayoría de los tipos celulares ováricos. Las HT afectan la esteroideogénesis e inhiben la aromatasa, pero estimulan el crecimiento folicular. El hipotiroidismo produce hiperprolactinemia, que induce irregularidades en el ciclo, y en la rata, pseudopreñez, hipofunción del eje GH-IGF y aumento de la aromatasa y estradiol circulante. El hipertiroidismo produce un aumento temprano en la secreción preovulatoria de FSH, ...
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The rat prolactin receptor (PRL-R) exists in two forms, which differ in the length of the cytoplasmic domains, tissue distribu-tion, and biological activity. The short form predominates in liver while the long form is prevalent in mammary... more
The rat prolactin receptor (PRL-R) exists in two forms, which differ in the length of the cytoplasmic domains, tissue distribu-tion, and biological activity. The short form predominates in liver while the long form is prevalent in mammary gland. We have compared activation by PRL of the JAK2-STAT pathway (protein tyrosine phosphorylation and STAT5 activation) in mammary gland and liver in an in vivo rat model of induction of lactogen-esis by PRL injections, and we have studied the relative propor-tion of both forms of the receptor in these tissues by reverse transcription-polymerase chain reaction. Rats were ovario-hys-terectomized on Day 19 of pregnancy, treated with bromocrip-tine, subsequently injected with 250 g ovine PRL i.p. on Day 20, and killed 0-12 h after. Western blots of solubilized mam-mary gland and liver membranes immunoprecipitated with anti-
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Mendoza province, in central west Argentina, is considered among the high-risk provinces for vector transmission of Trypanosoma cruzi, the causative agent of Chagas disease. Extensive goat farming is common in large parts of rural... more
Mendoza province, in central west Argentina, is considered among the high-risk provinces for vector transmission of Trypanosoma cruzi, the causative agent of Chagas disease. Extensive goat farming is common in large parts of rural Mendoza, and goats may act as a reservoir for this parasite. The objective of this study was to determine infection rates, parasite loads, and seasonal variation of these parameters in T. cruzi infection in goats from rural areas of three departments of Mendoza. A total of 349 peripheral blood samples with EDTA / guanidine were analyzed from goats on 11 farms (three in Lavalle, three in San Carlos, and five in Malargüe department) in spring of 2014, 2015, and 2016; and in fall of 2015 and 2016 (only Malargüe). DNA was extracted using a Phenol: Chloroform: Isoamyl protocol. The detection and quantification of T. cruzi was performed through qPCR amplification using satellite oligonucleotides. Of the 349 blood samples, 267 (77%) were positive, with parasite loads ranging between <0.10 and 10.90 par-eq/mL (median 0.10). In spring, frequencies of infection in the three departments ranged between 86% and 95%, but differences were not significant. Median parasite loads were higher in Lavalle than in the other departments, while those in goats from San Carlos were consistently low. The frequency of infection and parasite loads in Malargüe were significantly higher in spring than in fall. This seasonal variation may have been related to a reduced nutritional status and impaired immune response of goats in spring. In conclusion, the high proportion of positive goats confirms the persistence of T. cruzi in rural Mendoza.
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The effect of para-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, on prolactin release was studied in rats on the day of pro-oestrus and at the end of pregnancy (day 19). The surges of prolactin normally seen in the... more
The effect of para-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, on prolactin release was studied in rats on the day of pro-oestrus and at the end of pregnancy (day 19). The surges of prolactin normally seen in the afternoon of pro-oestrus in intact rats and in rats ovariectomized on dioestrous day 2 and primed with oestrogen were significantly inhibited by pCPA treatment. Administration of 5-hydroxy-tryptophan reversed the inhibitory action of pCPA on prolactin release. Treatment with progesterone also completely reversed the inhibitory effect of pCPA on prolactin release in pro-oestrous rats and partially reversed it in ovariectomized oestrogen-treated rats. Ovariectomy on day 19 of pregnancy induced a significant release of prolactin 12 and 24 h later. Administration of pCPA on day 18 of pregnancy produced a marked increase in serum concentrations of prolactin on days 19 and 20 in rats left intact or ovariectomized on day 19. Administration of 5-hydroxy-tryptop...
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... ANDES, SAN JUAN, ARGENTINA FACUNDO CABEZAS CARTES 1, JORGELINA BORETTO 1,2, JUAN CARLOS ACOSTA 3, GRACIELA JAHN 4, GRACIELA BLANCO 3, ALEJANDRO LASPIUR 3, NORA IBARGÜENGOYTÍA 1,2 1 ...
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In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system,... more
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect. Estrogen/ERα signaling induced an increase of Th17 cells in lymph nodes as well as the expression of its correspondent chemokine receptor CCR6 during collagen induced arthritis acute phase. High levels of anti- DNA antibodies and increased mortality was observed when given high E and prolactin doses to NZB/NZW mice, as compared with mice receiving low E and prolactin doses, or high E and low prolactin doses. Intracellular progesterone receptors have been detected in TCD4cells but ...
Research Interests: Immunology, Autoimmunity, Humans, Prolactin, Mice, and 5 moreFemale, Animals, Male, T lymphocytes, and B Lymphocytes
Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL... more
Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-in...
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Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are... more
Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cell...
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BackgroundProviding the context for the evolution of life-history traits, habitat features constrain successful ecological and physiological strategies. In vertebrates, a key response to life’s challenges is the activation of the Stress... more
BackgroundProviding the context for the evolution of life-history traits, habitat features constrain successful ecological and physiological strategies. In vertebrates, a key response to life’s challenges is the activation of the Stress (HPA) and Gonadal (HPG) axes. Much of the interest in stress ecology is motivated by the desire to understand the physiological mechanisms in which the environment affects fitness. As reported in the literature, several intrinsic and extrinsic factors affect variability in hormone levels. In both social and non-social animals, the frequency and type of interaction with conspecifics, as well as the status in social species, can affect HPA axis activity, resulting in changes in the reproductive success of animals. We predicted that a social environment can affect both guanaco axes by increasing the secretion of testosterone (T) and Glucocorticoid (GCs) in response to individual social interactions and the energetic demands of breeding. Assuming that pr...
The activity of cytosolic NADP-linked isocitrate dehydrogenase (ICDH) in rat liver was determined. The administration of 2-bromo-alpha-ergocryptine (CB-154) to male rats produced a significant increase of the enzyme activity and a... more
The activity of cytosolic NADP-linked isocitrate dehydrogenase (ICDH) in rat liver was determined. The administration of 2-bromo-alpha-ergocryptine (CB-154) to male rats produced a significant increase of the enzyme activity and a decrease of serum prolactin (PRL) levels in relation to control animals. Male rats 21 days after castration had lower levels of serum prolactin and higher activity of the enzyme than controls. Injection of PRL to castrated male rats lowered the enzymatic activity to control values. In intact rats injected with prolactin, the activity of the enzyme also decreased. Female rats were separated into the following groups: (a) virgins; (b) rats on day 15 of lactation; (c) ovariectomized rats. The enzymatic activity was similar in the different groups, but significantly higher than in male rats. However, serum PRL was significantly increased in 15 days lactating rats and decreased in ovariectomized ones in relation to virgins. We conclude that PRL regulates hepatic ICDH activity in male, but not in female rats. Incubation of isolated hepatocytes from intact or castrated male rats maintained the difference in ICDH activity observed in vivo, while there were no differences in ICDH activity in non-parenchymal cells. Addition of PRL, CB-154, androgens or antiandrogens to isolated hepatocytes from intact and castrated rat, had no effect on the ICDH activity, suggesting that the effect of PRL is exerted at the transcriptional level.
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The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current... more
The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current study was to evaluate the effects of pre- and postnatal exposure to 2,4-D on rat ventral prostate (VP). Pregnant rats were exposed daily to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the treated groups (n = 8) were fed with a 2,4-D added diet until sacrificed by decapitation on postnatal day (PND) 45, 60, or 90. Morphometric studies were performed and androgen receptor (AR) protein levels in the VP were determined. AR, insulin-like growth factor-I (IGF-1) and insulin-like growth factor-I receptor (IGF-1R) mRNA expression in the VP along with testosterone (T), dihydroxytestosterone (DHT), growth hormone (GH) and IGF-1 serum levels were also determined to ascertain whether these parameters were differentially affected. Results of this study showed that 2,4-D exposure during gestation and until adulthood altered development of the prostate gland in male rats, delaying it at early ages while increasing its size in adults, indicate that 2,4-D could behave as endocrine disruptors (EDs).
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Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to... more
Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells. Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells. To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data. Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth.