Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intracerebroventricular (icv) infusion of four neuropeptides on female sexual behavior were examined in the female musk shrew (Suncus murinus). In the first experiment, (icv) infusion of 100 ng of the mammalian form of gonadotropin-releasing hormone (mGnRH) facilitated rapid display of receptivity. Gonadotropin-releasing hormone-infused females had shorter latencies to rump present and tail wag, compared with controls. In a second experiment, icv administration of the other form of GnRH present in musk shrew brain, the chicken GnRH-II form, produced no changes in female behavior relative to the control condition. In Experiment 3, icv delivery of corticotropin-releasing hormone (CRH) facilitated female sexual behavior, relative to vasopressin and controls. The females treated with CRH had shorter latencies to display rump present, tail wag, and for the receipt of the first missed intromission compared with females in the other treatment groups. Vasopressin increased female scent marking relative to that of CRH-treated females. These data indicate that neurohormones of the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-adrenal axes can facilitate reproductive behavior in S. murinus.
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PMID:Effects of gonadotropin-releasing hormones, corticotropin-releasing hormone, and vasopressin on female sexual behavior. 1086 84

The gas nitric oxide is a messenger in brain signaling. In the hypothalamo-hypophyseal system nitric oxide is involved in the control of the expression and/or release of peptide hormones (corticotropin-releasing hormone, gonadotropin-releasing hormone, vasopressin and oxytocin). Nitric oxide synthase (NOS), the enzyme generating nitric oxide, is abundantly present in the magnocellular nuclei of the rat hypothalamus. Its localization in the human hypothalamus is less well studied. Hence, we investigated the anatomical distribution of neuronal nitric oxide synthase in the human supraoptic nucleus by use of immunohistochemical and enzyme histochemical techniques. The immunohistochemical localization of NOS was studied in 31 matched human hypothalami (13 control cases, eight depressed patients and ten schizophrenics). NADPH-diaphorase studies were carried out on seven additional hypothalami (three normal brains, four schizophrenics). Apparent inter-individual differences exist with regard to the occurrence of the enzyme in supraoptic neurons. In a majority of cases no immunostaining or histochemical reaction for the enzyme was observed. In seven cases (three controls, two schizophrenics, two depressives) a population of nitrergic nerve cells was seen in the dorsomedial part of the nucleus. This group of cells also stained for NADPH-diaphorase. Also, there were a few NOS-immunopositive neurons scattered throughout the nucleus. Additionally, thin NADPH-diaphorase positive fibers were observed to cross the nucleus. Our data show that, unlike the rat, the human supraoptic nucleus contains only a small number of nitrergic neurons. No correlation was found between the expression of the enzyme in supraoptic neurons and the psychiatric status of the patients.
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PMID:Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study. 1111 9

Aminopeptidases (APs) play a major role in the metabolism of circulating and local peptides, such as angiotensins and vasopressin, substances involved in the control of blood pressure and water balance. In the present work, we studied the influence of dehydration on angiotensinases and vasopressin-degrading activity. Since sex differences may exist in the regulation of water balance by angiotensin II and differential sexual steroid modulation of vasopressin secretion, in response to osmotic stimulation have been reported, gonadotropin releasing hormone (GnRH)-degrading activity was also analysed in serum, neurohypophysis and adrenal glands of male and female rats. Our results did not suggest sex differences in the response to changes in osmolality. GnRH-degrading activity decreased in serum of dehydrated males and females, which suggests a longer action of the peptide under these conditions. In neurohypophysis, there was an increase in the activity of aminopeptidase A (APA), the enzyme responsible for the metabolism of angiotensin II to angiotensin III. This occurs with a decrease in alanyl aminopeptidase activity, which would lead to a prolonged action of angiotensin III by reduction of its metabolism. In adrenals of dehydrated animals, the results would imply a high degree of metabolism of angiotensin III and vasopressin.
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PMID:Aminopeptidase activities after water deprivation in male and female rats. 1149 96

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture. Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.
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PMID:Neuroendocrine abnormalities in patients with traumatic brain injury. 1153 74

Vasotocin (VT, the antidiuretic hormone of birds) is synthesized by diencephalic magnocellular neurons projecting to the neurohypophysis. In addition, in male quail and in other oscine and non-oscine birds, a sexually dimorphic group of VT-immunoreactive (ir) parvocellular neurons is located in a region homologous to the mammalian nucleus of the stria terminalis, pars medialis (BSTm) and in the medial preoptic nucleus (POM). These cells are not visible in females. VT-ir fibers are present in many diencephalic and extradiencephalic locations. Quantitative morphometric analyses demonstrate that, in quail, these elements are expressed in a sexually dimorphic manner (males>females) in regions involved in the control of different aspects of reproduction: i.e., the POM (copulatory behavior), the lateral septum (secretion of gonadotropin-releasing hormone [GnRH]), the nucleus intercollicularis (control of vocalizations), and the locus coeruleus (the main noradrenergic center of the avian brain). In many of these regions, VT-ir fibers are closely related to aromatase-ir, GnRH-ir, or estrogen receptor-expressing neurons. This dimorphism has an organizational nature: administration of estradiol-benzoate to quail embryos (a treatment that abolishes male sexual behavior) results in a dramatic decrease of the VT-immunoreactivity in all sexually dimorphic regions of the male quail brain. Conversely, the inhibition of estradiol (E2) synthesis during embryonic life (a treatment that stimulates the expression of male copulatory behavior in adult testosterone (T)-treated females) results in a male-like distribution of VT-ir cells and fibers. Castration markedly decreases the immunoreactivity in both the VT-immunopositive elements of the BSTm and the innervation of the SL and POM, whereas T-replacement therapy restores the VT immunoreactivity to a level typical of intact birds. These changes reflect modifications of VT mRNA concentrations (and probably synthesis) as demonstrated by in situ hybridization and they are paralleled by similar changes in male copulatory behavior (absent in castrated male quail, fully expressed in CX+T males). The aromatization of T into estradiol (E2) also controls VT expression and, in parallel limits the activation of male sexual behavior by T. In castrated male quail, the restoration by T of the VT immunoreactivity in POM, BSTm and lateral septum could be fully mimicked by a treatment with E2, but the androgen 5alpha-dihydrotestosterone (DHT) had absolutely no effect on the VT immunoreactivity in these conditions. At the doses used in this study, DHT also did not synergize with E2 to enhance the density of VT immunoreactive structures. Systemic or i.c.v. injections of VT markedly inhibit the expression of all aspects of male sexual behavior. VT, presumably, does not simply represent one step in the biochemical cascade of events that is induced by T in the brain and leads to the expression of male sexual behavior. Androgens and estrogens presumably affect reproductive behavior both directly, by acting on steroid-sensitive neurons in the preoptic area, and indirectly, by modulating peptidergic (specifically vasotocinergic) inputs to this and other areas. The respective contribution of these two types of actions and their interaction deserves further analysis.
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PMID:Steroid-induced plasticity in the sexually dimorphic vasotocinergic innervation of the avian brain: behavioral implications. 1174 86

Aminopeptidases (APs) are important regulators of peptides directly involved in water homeostasis such as angiotensins (Ang) and vasopressin (AVP). Sex differences in water balance and differences in the effects of gonadal steroids on osmotic stimulation of vasopressin secretion have been reported. Since sex steroids may be involved, the gonadotropin response to osmotic stimuli may be different between males and females. The purpose of this study was to determine the behavior of angiotensinases, vasopressin-degrading activity and gonadotropin-releasing hormone (GnRH)-degrading activity in the cortex and medulla of the kidney of dehydrated male and female rats. In the renal cortex, our results demonstrated an increase in Ang III-degrading activity in dehydrated males but not in females. This response may lead to an increased formation of Ang IV. This occurs with an increase in AspAP activity (which metabolizes Ang I to des-Asp(1)-Ang I), with no changes in Ang II-degrading activity and also with increased levels of AVP-degrading activity in dehydrated animals. These results may suggest an increased cortical blood flow due to enhanced formation of Ang IV together with reduced availability of the vasoconstrictor agents Ang II and AVP in the renal cortex of dehydrated males. The results obtained in the renal medulla suggest the inhibition of the metabolism of Ang I to des-Asp(1)-Ang I, together with a reduced metabolism of Ang II and AVP in dehydrated males but not in females. These results suggest a prolonged action of Ang II and AVP, which could stimulate sodium and water reabsorption in the medulla of dehydrated males. Changes in APs after dehydration occur preferentially in males, which may explain in part the reported sex differences in water homeostasis. The present results suggest a physiologically relevant role for AP activities in water homeostasis.
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PMID:Effects of dehydration on renal aminopeptidase activities in adult male and female rats. 1204 7

Dwyer has suggested that peptide receptors evolved from self-aggregating peptides so that peptide receptors should incorporate regions of high homology with the peptide ligand. If one considers self-aggregation to be a particular manifestation of molecular complementarity in general, then it is possible to extend Dwyer's hypothesis to a broader set of peptides: complementary peptides that bind to each other. In the latter case, one would expect to find homologous copies of the complementary peptide in the receptor. Thirteen peptides, 10 of which are not known to self-aggregate (amylin, ACTH, LHRH, angiotensin II, atrial natriuretic peptide, somatostatin, oxytocin, neurotensin, vasopressin, and substance P), and three that are known to self-aggregate (insulin, glucagon, and gastrin), were chosen. In addition to being self-aggregating, insulin and glucagon are also known to bind to each other, making them a mutually complementary pair. All possible combinations of the 13 peptides and the extracellular regions of their receptors were investigated using bioinformatic tools (a total of 325 combinations). Multiple, statistically significant homologies were found for insulin in the insulin receptor; insulin in the glucagon receptor; glucagon in the glucagon receptor; glucagon in the insulin receptor; and gastrin in gastrin binding protein and its receptor. Most of these homologies are in regions or sequences known to contribute to receptor binding of the respective hormone. These results suggest that the Dwyer hypothesis for receptor evolution may be generalizable beyond self-aggregating to complementary peptides. The evolution of receptors may have been driven by small molecule complementarity augmented by modular evolutionary processes that left a "molecular paleontology" that is still evident in the genome today. This "paleontology" may allow identification of peptide receptor sites.
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PMID:Molecular complementarity III. peptide complementarity as a basis for peptide receptor evolution: a bioinformatic case study of insulin, glucagon and gastrin. 1229 71

In order to fulfill their roles in neuroendocrine regulation, specific hypothalamic neurons are devoted to produce and deliver biologically active peptides to the pituitary gland. The biosynthesis and release of peptides are strictly controlled by afferents to these hypothalamic neurons. Cell-specific expression and biosynthetic regulation largely relies on transcription from the gene promoter for which the 5(')-flanking regions of the peptidergic genes contain essential elements. Cell-specific transcription factors employ these regulatory elements to exert their control over the expression of the peptidergic gene. This article explores the properties of regulatory elements of the major hypothalamic peptides, somatostatin, growth hormone-releasing hormone, gonadotropin-releasing hormone, thyrotropin-releasing hormone, corticotropin-releasing hormone, vasopressin and oxytocin, and the transcription factors acting on them. These transcription factors are often endpoints of signal transduction pathways that can be activated by neurotransmitters or steroid hormones. Others are essential to provide cell-specific expression of the peptidergic gene during development and mature regulation.
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PMID:Regulation of gene promoters of hypothalamic peptides. 1238 30

Recent advances in the development of potent and selective peptide and non-peptide ligands for peptidergic receptors are anticipated to help further unravel the roles of class I and II G-protein-coupled receptors in the pathogenesis of human diseases and to accelerate the clinical utility of small molecule peptidomimetics. Peptidomimetic drug discovery directed towards somatostatin agonists, urotensin II antagonists, gonadotropin-releasing hormone antagonists, neurotensin and complement C5a modulators, melanocortin-4 agonists and vasopressin V(2) agonists has achieved success through integration of conformational-based drug design, site-directed mutagenesis, screening, combinatorial chemistry and classical medicinal chemistry. Acceptance that discreet ensembles of secondary structural motifs underpin the interactions of peptides with their cognate receptors has enabled the development of molecules which mimic or stabilize such pharmacophores.
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PMID:Clinically validated peptides as templates for de novo peptidomimetic drug design at G-protein-coupled receptors. 1455

We report the first isolation of progenitor cells from the hypothalamus, a derivative of the embryonic basal plate that does not exhibit neurogenesis postnatally. Neurons derived from hypothalamic progenitor cells were compared with those derived from progenitor cultures of hippocampus, an embryonic alar plate derivative that continues to support neurogenesis in vivo into adulthood. Aside from their different embryonic origins and their different neurogenic potential in vivo, these brain regions were chosen because they are populated with cells of three different categories: Category I cells are generated in both hippocampus and hypothalamus, Category II cells are generated in the hypothalamus but are absent from the hippocampus, and Category III is a cell type generated in the olfactory placode that migrates into the hypothalamus during development. Stem-like cells isolated from other brain regions, with the ability to generate neurons and glia, produce neurons of several phenotypes including gabaergic, dopaminergic, and cholinergic lineages. In the present study, we extended our observations into neuroendocrine phenotypes. The cultured neural precursors from 7-week-old rat hypothalamus readily generated neuropeptide-expressing neurons. Hippocampal and hypothalamic progenitor cultures converged to indistinguishable populations and produced neurons of all three categories, confirming that even short-term culture confers or selects for immature progenitors with enough plasticity to elaborate neuronal phenotypes usually inhibited in vivo by the local microenvironment. The range of phenotypes generated from neuronal precursors in vitro now includes the peptides found in the neuroendocrine system: corticotropin-releasing hormone, growth hormone-releasing hormone, gonadotropin-releasing hormone, oxytocin, somatostatin, thyrotropin-releasing hormone, and vasopressin.
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PMID:Novel neuronal phenotypes from neural progenitor cells. 1504 27


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