Papers by A Quintanar-Stephano
OBJECTIVE—Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for th... more OBJECTIVE—Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sight-threatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men and test whether increased circulating PRL, by serving as a source of ocular vasoinhibins, can reduce the pathological RVP in diabetes. RESEARCH DESIGN AND METHODS—Serum PRL was evaluated in 40 nondiabetic and 181 diabetic men at various stages of DR. Retinal vasoinhibins were measured in rats rendered hyper-prolactinemic by placing two anterior pituitary grafts under the kidney capsule and in PRL receptor–null mice. RVP was determined in hyperprolactinemic rats subjected to the intraocular injection of vascular endothelial growth factor (VEGF) or made diabetic with streptozotocin. RESULTS—The circulating levels of PRL increased in diabetes and were higher in diabetic patients without retinopathy than in those with proliferative DR. In rodents, hyperprolactinemia led to vasoinhibin accumulation within the retina; genetic deletion of the PRL receptor prevented this effect, indicating receptor-mediated incorporation of systemic PRL into the eye. Hyperpro-lactinemia reduced both VEGF-induced and diabetes-induced increase of RVP. This reduction was blocked by bromocriptine, an inhibitor of pituitary PRL secretion, which lowers the levels of circulating PRL and retinal vasoinhibins.
Acta physiologica, pharmacologica et therapeutica latinoamericana : órgano de la Asociación Latinoamericana de Ciencias Fisiológicas y [de] la Asociación Latinoamericana de Farmacología, 1996
The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion of TSH, FSH-LH ... more The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion of TSH, FSH-LH and ACTH was studied in the rat. The pituitary response to EHE was assessed by measuring 131I uptake by the thyroid and by weight changes of the pituitary glands, thyroids, adrenals, ovaries and uteri. 131I uptake of the thyroid and weights of the pituitary, thyroid, adrenal and uterus increased in the treated rats, whereas ovarian weights were similar to control groups. These findings indicate that the EHE containes hypophysiotropic peptides which can stimulate the secretion of pituitary hormones in the rat.
Advances in Neuroimmune Biology, 2015
Journal of investigational allergology & clinical immunology, 2008
Activation of mast cells (MCs) via aggregation of immunoglobulin E (IgE) bound to its high affini... more Activation of mast cells (MCs) via aggregation of immunoglobulin E (IgE) bound to its high affinity receptor (FcepsilonRI) results in release of inflammatory mediators from secretory granules. Histamine is one of the critical biological mediators released in the allergic response. Synaptosomal-associated protein of 23 kDa (SNAP-23) and syntaxin 4 are plasma membrane proteins that have been associated with exocytosis in MCs. Studies with monoclonal IgEs indicate that binding of IgE to FcepsilonRI induces molecular and biological changes in The aim of this study was to investigate changes in the expression of SNAP-23 and syntaxin 4 by MCs following rat sensitization with ovalbumin (OVA). In addition, we assessed whether these proteins were involved in histamine secretion. SNAP-23 and syntaxin 4 expression was analyzed by Western blot using MCs from control and sensitized animals. Successful sensitization was confirmed based on the passive cutaneous anaphylaxis reaction. To test the ro...
Endocrine, 1996
The effect of removing the posterior and neuro-intermediate lobes (PLX) of the pituitary gland of... more The effect of removing the posterior and neuro-intermediate lobes (PLX) of the pituitary gland of lactating rats was determined on both suckling-induced release and transformation of prolactin (PRL), and on regionalization of PRL release. Sixteen hours, or 1 or 4 d after either PLX or sham surgery, acute (15-min) suckling was applied. Also, regionalization of PRL release was analyzed by incubating the central and peripheral regions of APs from nonsuckled rats. Plasma PRL was analyzed by radioimmunoanalysis (RIA), whereas anterior pituitary (AP) PRL content and in vitro released PRL were determined by polyacrylamide gel electrophoresis. Plasma PRL increased 25- to 30-fold after suckling in intact and sham, and 10- to 15-fold in 1- and 4-d PLX rats, but no change occurred on either 16-h PLX nonsuckled and suckled rats. Also, PRL transformation occurred in intact, sham, and 4-d PLX suckled rats, but not in 16-h sham, or in 16-h and 1-d PLX suckled rats. Finally, the higher secretion of PRL shown in vitro by the central region of APs from intact and sham was not observed in APs from PLX rats. These results show that PLX transiently depresses the suckling-regulated PRL transformation and release. Likewise, influences from the posterior and/or neuro-intermediate lobes may determine regionalization of PRL release.
Journal of Neuroscience, 2014
We explored whether the hormone prolactin provides trophic support to retinal cells, thus protect... more We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.
Parasite Immunology, 2011
The neuro-immune network, in which the vagus nerve is involved, provides feedback between its aff... more The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-c and increased numbers of IL-10 and IFN-c-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.
Journal of Endocrinology, 2011
Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this ... more Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the ratelimiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo-and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.
Journal of Endocrinology, 2005
Acute experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central n... more Acute experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system, mediated by T lymphocytes. Immunization of Lewis rats with myelin antigens suspended in complete Freund's adjuvant induces EAE. In a previous study on rats we have found that neurointermediate pituitary lobectomy (NIL) decreased both the humoral and cell-mediated immune responses. Here we investigated the effect of NIL on the incidence and severity of EAE and on the function of the hypothalamic-pituitary-adrenal axis in Lewis rats. NIL, hypophysectomized (Hypox) and sham-operated (Sham) rats were immunized s.c. with guinea-pig brain extract suspended in complete Freund's adjuvant. Untreated rats were used as controls. Water intake, body weight gain, clinical and histopathologic incidence and severity of EAE were evaluated in the operated groups. On killing, plasma adrenocorticotropin and corticosterone levels were measured and adrenals, thymuses and spleens were weighed. Histopathologic lesions were counted in the brain and spinal cord. Water intake and body weight gain were significantly decreased in Sham and Hypox animals with EAE whereas higher intakes persisted in the NIL group. Plasma levels of adrenocorticotropin were within the normal range whereas corticosterone levels increased in Sham and occasionally in NIL animals. Thymus weights were decreased in NIL and Hypox groups. The clinical and histopathologic incidence and severity of EAE were significantly decreased in NIL animals as compared with Sham and Hypox rats. We concluded that NIL affects the cell-mediated immune response and plays a role in the development and progression of EAE in the Lewis rat.
General and Comparative Endocrinology, 2007
Sexual dimorphism in lacrimal gland (LG) gene expression is believed to be due to direct inductiv... more Sexual dimorphism in lacrimal gland (LG) gene expression is believed to be due to direct inductive effects of androgens mediated by androgen receptors (AR) but hypophysectomy dramatically curtails these inductive effects. Since, functional estrogen receptors (ER) could not be detected in LG, estrogen effects on LG are believed to be indirectly mediated by changes in levels of pituitary hormones. We found that two lipocalins expressed in female hamster LG display an unusual and marked repression by both androgens and estrogens, which could be detected both at the level of transcripts and proteins. Here, we investigate whether these repressions, (i) require presence of pituitary and (ii) are mediated by androgen and estrogen receptors. Pituitary-ablation but not gonadectomy reduced LG weights in hamster. However, both pituitary-ablation and gonadectomy induced abundant expression of the LG lipocalins, which were markedly repressed by androgen or estrogen treatment. AR- and ER-antagonists prevented these repressions and only ER-alpha- but not ER-beta-specific agonist could mimic the estrogenic repression. AR transcript and protein and ER-alpha transcript were also detected in hamster LG. Thus, pituitary factors are neither essential for the expression of these LG lipocalins nor for their estrogenic or androgenic repressions and these repressions are very likely mediated by functional ER and AR present in LG.
Diabetes, 2010
OBJECTIVE-Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for th... more OBJECTIVE-Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sightthreatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men and test whether increased circulating PRL, by serving as a source of ocular vasoinhibins, can reduce the pathological RVP in diabetes.
International Journal of Experimental Pathology, 2010
Journal of Endocrinology, 1997
The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs a... more The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin\p=n-\eosin-stained or periodic acid\p=n-\ Schiff\p=n-\hematoxylin-stainedpituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T4 (0\m=.\5, 3 or 10 \g=m\g i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm2 areas at a magnification of \m=x\ 1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0\ m=. \ 5\ g=m\gT4 alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T4, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T4 had a significant synergistic effect on pituitary mitoses in a T4 dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12\m=.\5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28\m=.\5%and
Anatomia, Histologia, Embryologia, 2009
Newborn children of diabetic mothers have an increased morbidity and mortality because of respira... more Newborn children of diabetic mothers have an increased morbidity and mortality because of respiratory distress syndrome. We study lung histogenesis during intrauterine development of offspring of diabetic Sprague-Dawley rats at 18, 19 and 21 days of gestation (DG). Pregnant rats were grouped into diabetic (streptozotocin-induced), citrate, and control groups; five female and five male offspring were selected randomly from each group at 18, 19 and 21 DG, and a biopsy of the lung was taken and processed in paraffin for histological examination. The biopsy for the transmission electron microscopy (TEM) analysis was taken at 21 days. A delay in alveolization of the offspring at 18, 19 and 21 days of the diabetic group was observed, which was confirmed at TEM level, and also less quantity of protein D associated to surfactant in diabetic group was detected (P < 0.001). The foetuses of the diabetic group presented a delay in lung histogenesis and in differentiation of the type II pneumocytes cells, but conserved the proportion with a decrease in 50% of pneumocytes, accompanied by a diminish of protein D associated to surfactant factor.
Infection and …, 2006
The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals ... more The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, reduction of gastric secretion and intestinal absorption, and increased susceptibility to infections. To our knowledge, there are no studies on the humoral immune response of the gut-associated lymphoid tissue after HYPOX.
Journal of Physiology and Biochemistry, 2010
In rats, hypophysectomy (HYPOX) or neurointermediate pituitary lobectomy (NIL) reduce humoral and... more In rats, hypophysectomy (HYPOX) or neurointermediate pituitary lobectomy (NIL) reduce humoral and cell-mediated immune responses. However, to our knowledge, the differences in the effects of anterior versus posterior pituitary hormones on the immune responses have not been studied to date. We compared in rats, the effects of sham surgery (SHAM), HYPOX, and NIL on humoral immune responses to T cell-independent
Endocrine Pathology, 2001
The incidence and histology of cysts in the adenohypophysis of adult male Wistar rats are reporte... more The incidence and histology of cysts in the adenohypophysis of adult male Wistar rats are reported. Of sixty pituitaries studied 13 of them (21.6%) presented a single cyst located in the pars distalis. The cysts varied in shape and size and were usually multilocular. Two of them were connected with the subdural space at the ventral surface of the adenohypophysis. Histology demonstrated that the cysts were filled with mucinous material and foamy macrophages and were lined by flat and cuboidal ciliated and nonciliated epithelial cells, goblet cells as well as several adenohypophysial endocrine cells such as somatotrophs, thyrotrophs, and gonadotrophs. The ciliated cells were the most numerous. Histologic and immunohistochemical studies of the uninvolved areas of the adenohypophysis showed no abnormalities and the weights and histology of the adenohypophyses and peripheral endocrine glands were within normal range, suggesting that the cysts did not impair the adenohypophysial endocrine activity. Although the morphogenesis of the cysts remained obscure, the histological and immunohistochemical findings support the hypothesis that during embryonic development, the future cysts coming from the pharyngeal epithelium is fused with the stomodeum before or during the formation of the Rathke's pouch.
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Papers by A Quintanar-Stephano