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)

Neurohypophysial hormones have been implicated in the control of anterior pituitary function, and oxytocin has been shown to stimulate gonadotrophin excretion and ovarian follicular development in certain species. To determine the role of neurohypophysial peptides in the control of gonadotrophin release, their actions on LH and FSH secretion were analysed in rats in vivo and in vitro. In adult female rats, administration of oxytocin during early pro-oestrus advanced the spontaneous LH surge and markedly increased peripheral LH levels at 15.00 h compared with control animals. In cultured pituitary cells from adult female rats, oxytocin and vasopressin elicited dose-related increases in LH and FSH release. Such responses were not affected by a potent gonadotrophin-releasing hormone (GnRH) antagonist that abolished GnRH agonist-induced release of LH and FSH. Oxytocin did not enhance GnRH agonist-stimulated gonadotrophin release to the same extent as it increased basal secretion, but at low concentrations of GnRH agonist the effects were additive. The gonadotrophin responses to oxytocin and vasopressin were inhibited by the specific neurohypophysial hormone antagonists, [d(CH2)5D-Ile2,Ile4,Arg8]vasopressin and [d(CH2)5Tyr (Me),Arg8]vasopressin. These results provide direct evidence that neurohypophysial hormones can stimulate gonadotrophin secretion through a receptor system distinct from the GnRH receptor. Such a mechanism could represent a complementary hypothalamic control system for long-term modulation of LH and FSH secretion by exerting a basal or tonic influence on gonadotrophin production.
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PMID:Gonadotrophin-releasing activity of neurohypophysial hormones: I. Potential for modulation of pituitary hormone secretion in rats. 250 72

GnRH binds to a specific G protein-coupled receptor in the pituitary to regulate synthesis and secretion of gonadotropins. Using RT-PCR and human pituitary poly(A)+ RNA as a template, the full-length GnRH receptor (wild type) and a second truncated cDNA characterized by a 128-bp deletion between nucleotide positions 522 and 651 were cloned. The deletion causes a frame shift in the open reading frame, thus generating new coding sequence for further 75 amino acids. The truncated cDNA arises from alternative splicing by accepting a cryptic splicing acceptor site in exon 2. Distinct translation products of approximately 45-50 and 42 kDa were immunoprecipitated from COS-7 cells transfected with cDNA coding for wild type GnRH receptor and the truncated splice variant, respectively. Immunocytochemical and enzyme-linked immunosorbent assay studies revealed a membranous expression pattern for both receptor isoforms. Expression of the splice variant, however, occurred at a significantly lower cell surface receptor density. In terms of ligand binding and phospholipase C activation, the wild type receptor showed characteristics of a typical GnRH receptor, whereas the splice variant was incapable of ligand binding and signal transduction. Coexpression of wild type and truncated proteins in transiently or stably transfected cells, however, resulted in impaired signaling via the wild type receptor by reducing maximal agonist-induced inositol phosphate accumulation. The inhibitory effect depended on the amount of splice variant cDNA cotransfected and was specific for the GnRH receptor because signaling via other G(q/11)-coupled receptors, such as the thromboxane A2, M5 muscarinic, and V1 vasopressin receptors, was not affected. Immunological studies revealed that coexpression of the wild type receptor and the truncated splice variant resulted in impaired insertion of the wild type receptor into the plasma membrane. Thus, expression of truncated receptor proteins may highlight a novel principle of specific functional inhibition of G protein-coupled receptors.
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PMID:Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor. 925 21

The influence of gonadotrophin-releasing hormone (GnRH) and its analogues (i.e., agonist and antagonist) on vasopressin (VP) release from the rat hypothalamo-neurohypophysial (H-N) system was studied both in vitro and in vivo. Additionally, it was determined whether the possible response of vasopressinergic neurones to these peptides could be modified by melatonin through a cAMP-dependent mechanism. In this study we demonstrate, for the first time, that the highly selective GnRH agonist (i.e., [Des-Gly(10),D-His(Bzl)(6),Pro-NHEt(9)]-LHRH; histrelin) stimulates the release of VP from the rat H-N system, while native GnRH and its antagonist remain inactive in modifying this process in vitro. Melatonin significantly inhibited basal and histrelin-induced release of VP in vitro, but displayed no significant influence on VP secretion when GnRH or its antagonist were present in a medium. Melatonin fully suppressed forskolin-stimulated VP release from the rat H-N system. On the other hand, addition of forskolin to a medium containing both histrelin and melatonin did not further alter the inhibitory influence of melatonin on the histrelin-dependent release of VP in vitro. After intracerebroventricular (i.c.v.) infusion of native GnRH or its agonist, blood plasma VP concentration was significantly higher than in control animals, which was accompanied by decreased content of the hormone in the neurohypophysis. Intravenous (i.v.) injection of melatonin did not change, in any subgroup, blood plasma VP concentration, when compared to the vehicle-injected rats. However, the neurohypophysial levels of the hormone were significantly higher after melatonin injection in control, GnRH- and histrelin-infused animals. Our present results suggest that activation of the GnRH receptor in the hypothalamus is involved in stimulation of VP secretion from the rat H-N system. We have also shown that melatonin, at a concentration close to its physiological level in the blood, significantly reduces the in vitro response of vasopressinergic neurones to a GnRH agonist - histrelin; this effect of melatonin could be mediated through intracellular processes that involve, among others, the cAMP-dependent mechanism.
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PMID:Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of gonadotrophin-releasing hormone (GnRH), its analogues and melatonin. 2081 74

Gonadotropin-releasing hormone (GnRH) plays a central role in vertebrate reproduction. The evolutionary origin of this neuropeptide and its receptor is not obvious, but the advent of genomics makes it possible to examine the roots of GnRH and delve deeper into its ancestral relationships. New peptide sequences identified in invertebrates from annelids to tunicates reveal GnRH-like peptides of 10-12 amino acids. Structural conservation suggests homology between the 15 known invertebrate peptides and the 15 known vertebrate GnRHs. The functions of the invertebrate GnRH-like peptides are not necessarily related to reproduction. We suggest that structurally related families of invertebrate peptides including corazonin and adipokinetic hormone (AKH) form a superfamily of neuropeptides with the GnRH family. GnRH receptors have also been identified in invertebrates from annelids to tunicates suggesting that the origin of GnRH and its receptor extends deep in evolution to the origin of bilaterian animals. To resolve the relationship of invertebrate and vertebrate receptors, we conducted large-scale phylogenetic analysis using maximum likelihood. The data support a superfamily that includes GnRH, AKH and corazonin receptors derived from both published sequences and unpublished gene model predictions. Closely related to the GnRHR superfamily is the vasopressin/oxytocin superfamily of receptors. Phylogenetic analysis suggests a shared ancestry with deep roots. A functional role for GnRH in vertebrates or invertebrates leads to questions about the evolutionary origin of the pituitary. Our analysis suggests a functioning pituitary was the result of genomic duplications in early vertebrates.
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PMID:Evolution of GnRH: diving deeper. 2118 90

Mutations cause protein folding defects that result in cellular misrouting of otherwise functional proteins. Such mutations are responsible for a wide range of disease states, especially among G-protein coupled receptors. Drugs which serve as chemical templates and promote the proper folding of these proteins are valuable therapeutic molecules since they return functional proteins to the proper site of action. Small molecules have been identified that are able to function as pharmacological chaperones or "pharmacoperones" and stabilize the correct conformations of their target proteins with high specificity. Most of these are also agonists or antagonists of the proteins of interest, complicating potential therapeutic use. This is due, in part, to the fact that the majority of these were discovered during high-throughput screening campaigns using assays designed to detect agonists and antagonists, rather than compounds which improve the trafficking of misrouted mutants. The assays described in this report are designed specifically to identify compounds which result in the reactivation and correct trafficking of misfolded gonadotropin releasing hormone receptor and vasopressin type 2 receptor mutants, rather than those which act as agonists directly. The system reported is a generalizable approach amenable to use in automated (robotic) high-throughput screening efforts and can be used to identify compounds which affect protein conformation without necessarily acting as direct agonists or antagonists.
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PMID:Therapeutic rescue of misfolded/mistrafficked mutants: automation-friendly high-throughput assays for identification of pharmacoperone drugs of GPCRs. 2335 31

Phoenixin is an amidated neuropeptide, which is widely distributed in brain and periphery regions and is known for its key role in reproduction. Phoenixin-14 (PNX-14), one of the endogenous active isoforms, was reported to regulate pituitary gonadotrophin secretion by increasing the expression of the GnRH receptor mRNA. Studies showed that GnRH could regulate brain responses to anxiety. However, the role of PNX-14 in anxiety was largely unclear. Here, we investigated that the effects of PNX-14 in anxiety-related behavior in adult mice via the open field and elevated plus maze. PNX-14 was administered intracerebroventricularly (i.c.v.) in different doses (5, 10, 25 and 50 nmol), and dose-dependently induced anxiolytic effects. Then this anxiolytic action was presented after PNX-14 injected into the anterior hypothalamic area (AHA), while PNX-14 infused into the amygdala did not exert anxiolytic effects. GnRH receptor antagonist (Cetrorelix) could significantly antagonize the anxiolytic effects of PNX-14, while Atosiban, a competitive vasopressin/oxytocin receptor antagonist could not. Moreover, PNX-14 could significantly lower the core temperature and Cetrorelix could block this effect of PNX-14. Additionally, the AHA infusion of PNX-14 (5 nmol) increased the expression level of the GnRH mRNA in the hypothalamus and plasma concentrations of GnRH. Similarly, i.c.v. injection of PNX-20 also reduced the core temperature and exerted anxiolytic effects. Taken together, centrally injected PNX-14 generates anxiolytic effects in mice, via the activation of the AHA GnRH system.
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PMID:Effects of Phoenixin-14 on anxiolytic-like behavior in mice. 2568 46

Ascidians are the closest phylogenetic neighbors to vertebrates and are believed to conserve the evolutionary origin in chordates of the endocrine, neuroendocrine, and nervous systems involving neuropeptides and peptide hormones. Ciona intestinalis harbors various homologs or prototypes of vertebrate neuropeptides and peptide hormones including gonadotropin-releasing hormones (GnRHs), tachykinins (TKs), and calcitonin, as well as Ciona-specific neuropeptides such as Ciona vasopressin, LF, and YFV/L peptides. Moreover, molecular and functional studies on Ciona tachykinin (Ci-TK) have revealed the novel molecular mechanism of inducing oocyte growth via up-regulation of vitellogenesis-associated protease activity, which is expected to be conserved in vertebrates. Furthermore, a series of studies on Ciona GnRH receptor paralogs have verified the species-specific regulation of GnRHergic signaling including unique signaling control via heterodimerization among multiple GnRH receptors. These findings confirm the remarkable significance of ascidians in investigations of the evolutionary processes of the peptidergic systems in chordates, leading to the promising advance in the research on Ciona peptides in the next stage based on the recent development of emerging technologies including genome-editing techniques, peptidomics-based multi-color staining, machine-learning prediction, and next-generation sequencing. These technologies and bioinformatic integration of the resultant "multi-omics" data will provide unprecedented insights into the comprehensive understanding of molecular and functional regulatory mechanisms of the Ciona peptides, and will eventually enable the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of chordates.
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PMID:The significance of Ciona intestinalis as a stem organism in integrative studies of functional evolution of the chordate endocrine, neuroendocrine, and nervous systems. 2603 Nov 89