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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secreted peptide hormones and components of the steroidogenic machinery are molecules that are expressed usually in high amounts and in a time- and cell-specific fashion within the cells that give rise to the bovine corpus luteum. They thus serve as useful markers for the events occurring within the nuclei of these cells that result in differentiation and the expression of the specific luteal phenotype. We have studied the bovine genes of three such luteal products: oxytocin, the new relaxin-like factor (RLF), and the steroidogenic acute regulatory protein (StAR). The oxytocin gene is expressed in the granulosal cells of the preovulatory follicle and in the large luteal cells of the immediately resulting early corpus luteum. The RLF gene is a major thecal cell product in antral and atretic follicles. It is also transcribed in luteal cells, but only in the mid- to late ovarian cycle and in pregnancy, following a temporal pattern of expression very similar to that of relaxin in pigs. The StAR gene appears to be upregulated only in the mid- to late ovarian cycle, several days after the increase in steroidogenic enzymes associated with luteinization and progesterone production. All three genes make use of the transcription factor SF-1 (Ad4BP) and, although they all respond to LH activation of adenylate cyclase, none utilize CRE-linked systems. Specific transcriptional activation must involve other factors to encode the information for the widely diverse temporal and cellular patterns of gene expression for these three genes.
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PMID:Luteal peptides and their genes as important markers of ovarian differentiation. 1069 56

The ovarian hormone relaxin, in addition to its role in pregnancy, exerts an action on the brain to influence oxytocin and vasopressin secretion, water drinking, and cardiovascular function. Intravenous (i.v.) infusion of relaxin causes an acute water drinking response, confirming its role as a dipsogenic hormone. The aim of this study was to determine whether neurones in the lamina terminalis, which project to the hypothalamic paraventricular and supraoptic nuclei, are activated by elevated levels of circulating relaxin in conscious rats. Immunocytochemistry combined with retrograde neuronal tracing with cholera toxin B subunit conjugated to cholera toxin B (CTB-gold) was used to identify populations of neurones responding with elevated cells of Fos protein to i.v. relaxin administration and which project to these specific hypothalamic sites. Neurones exhibiting Fos were present in the outer parts of the subfornical organ (SFO), the dorsal part of the organum vasculosum (OVLT), the supraoptic nucleus and the paraventricular nucleus. These did not occur in control rats with i.v. infusions of isotonic saline. Approximately 90% of neurones concentrated in the outer parts of the SFO and in the dorsal OVLT showed both retrogradely transported CTB-gold and Fos in response to i.v. infusion of relaxin. These data support a role for relaxin acting on the brain to regulate body fluid and electrolyte homeostasis by activating neural pathways subserving water drinking, vasopressin and oxytocin secretion.
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PMID:Identification of efferent neural pathways from the lamina terminalis activated by blood-borne relaxin. 1132 53

Following a short history of hormonal contraception, the chemistry of compounds with progesterone-like action is explained and their steroid structures are drawn. The pharmacology of progesterone includes the following: 1) insures nidation of the ovum and maintenance of normal uterine tonicity during pregnancy; 2) alters the sensitivity of myometrium to oxytocin and relaxin near the term of pregnancy; 3) prevents ovulation in normal circumstances and in pregnancy; 4) interacts with troph-hormones of the pituitary and contributes to the normal course of cycle and its cessation during pregnancy; 5) exerts a protective effect on existing gravidity; 6) makes endometrium proliferate; 7) acts as a thermogen; and 8) together with estrogens, regulates the vaginal and cervical mucus production. Gestagens display similar effects, but relative potency of individual compounds varies widely. Nortestosterone derivatives have a marked antigonadotrophic action, whereas progesterone derivatives are devoid of it. Another difference between the 2 groups of compounds is their hormonal side effects. For example, nortestosterone derivatives being anabolisants are responsible for weight gain and possible viralization, effects not found experimentally with progesterone derivatives. Clinically, gestagens are called ovulation inhibitors. They affect sexual centers of diencephalon negatively. Endometrial and vaginal epithelium undergo specific transformations when under the influence of gestagens. Similarly, the cervical mucus usually decreases in quantity and increases in viscosity, hindering the migration of sperm. The claudogenic effect (postovulatory inhibition) is discussed. The most improtant extragenital alterations which occur in conjunction with gestagen therapy are blood coagulation changes. Withdrawal of gestagens results in a rebound effect, allowing for greater than normal fertility after cessation of therapy.
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PMID:Chemistry, pharmacology and clinical pharmacology of oral contraceptives. 1233 83

Oxytocin secretion from the posterior pituitary gland is increased during parturition, stimulated by the uterine contractions that forcefully expel the fetuses. Since oxytocin stimulates further contractions of the uterus, which is exquisitely sensitive to oxytocin at the end of pregnancy, a positive feedback loop is activated. The neural pathway that drives oxytocin neurons via a brainstem relay has been partially characterised, and involves A2 noradrenergic cells in the brainstem. Until close to term the responsiveness of oxytocin neurons is restrained by neuroactive steroid metabolites of progesterone that potentiate GABA inhibitory mechanisms. As parturition approaches, and this inhibition fades as progesterone secretion collapses, a central opioid inhibitory mechanism is activated that restrains the excitation of oxytocin cells by brainstem inputs. This opioid restraint is the predominant damper of oxytocin cells before and during parturition, limiting stimulation by extraneous stimuli, and perhaps facilitating optimal spacing of births and economical use of the store of oxytocin accumulated during pregnancy. During parturition, oxytocin cells increase their basal activity, and hence oxytocin secretion increases. In addition, the oxytocin cells discharge a burst of action potentials as each fetus passes through the birth canal. Each burst causes the secretion of a pulse of oxytocin, which sharply increases uterine tone; these bursts depend upon auto-stimulation by oxytocin released from the dendrites of the magnocellular neurons in the supraoptic and paraventricular nuclei. With the exception of the opioid mechanism that emerges to restrain oxytocin cell responsiveness, the behavior of oxytocin cells and their inputs in pregnancy and parturition is explicable from the effects of hormones of pregnancy (relaxin, estrogen, progesterone) on pre-existing mechanisms, leading through relative quiescence at term inter alia to net increase in oxytocin storage, and reduced auto-inhibition by nitric oxide generation. Cyto-architectonic changes in parturition, involving evident retraction of glial processes between oxytocin cells so they get closer together, are probably a response to oxytocin neuron activation rather than being essential for their patterns of firing in parturition.
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PMID:The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy. 1260 99

Induction of labor is common in obstetric practice. According to the most current studies, the rate varies from 9.5 to 33.7 percent of all pregnancies annually. In the absence of a ripe or favorable cervix, a successful vaginal birth is less likely. Therefore, cervical ripening or preparedness for induction should be assessed before a regimen is selected. Assessment is accomplished by calculating a Bishop score. When the Bishop score is less than 6, it is recommended that a cervical ripening agent be used before labor induction. Nonpharmacologic approaches to cervical ripening and labor induction have included herbal compounds, castor oil, hot baths, enemas, sexual intercourse, breast stimulation, acupuncture, acupressure, transcutaneous nerve stimulation, and mechanical and surgical modalities. Of these nonpharmacologic methods, only the mechanical and surgical methods have proven efficacy for cervical ripening or induction of labor. Pharmacologic agents available for cervical ripening and labor induction include prostaglandins, misoprostol, mifepristone, and relaxin. When the Bishop score is favorable, the preferred pharmacologic agent is oxytocin.
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PMID:Methods for cervical ripening and induction of labor. 1277 59

Relaxin decreases oxytocin-stimulated rat myometrial contractions in vitro. This study used pregnant relaxin-deficient (Rlx-/-) mice to investigate the interaction between relaxin, oxytocin receptor (OTR), and estrogen receptor (ER) expression in the myometrium. Myometrial OTRs were significantly decreased on gestation day 18.5 in Rlx-/- mice than in Rlx+/+ mice. An increase in ERalpha in Rlx+/+ mice at term was correlated with a decrease in ERbeta, which was not observed in Rlx-/- mice. Treatment of Rlx-/- mice with relaxin had no effect on OTR, LGR7, or ERalpha expression, but it caused a significant decrease in ERbetas.
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PMID:Oxytocin and estrogen receptor expression in the myometrium of pregnant relaxin-deficient (Rlx-/-) mice. 1595 92

Relaxin exhibits pleiotropic effects on reproductive and nonreproductive tissues; the signaling mechanisms underlying these functions are still not well understood. Activation of protein kinase A and several other signal-regulated protein kinases results in the phosphorylation of phospholipase C (PLC)-beta3 and inhibit Galpha(q)-stimulated PLC activity. Therefore, PLCbeta3 may be targeted by both contractant and relaxant signaling pathways in myometrium and play a critical role in the balance between them. PHM1 cells express mRNA for relaxin receptor LGR7, and relaxin inhibits oxytocin-stimulated PLC activity in these cells. Thus, this model system may be useful in delineating signaling pathways used by relaxin. Here, we present evidence that relaxin stimulates phosphorylation of PLCbeta3 in PHM1 cells.
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PMID:Pathways used by relaxin to regulate myometrial phospholipase C. 1595 22

Several factors participate in regulation of growth and development as well as angiogenesis of the uterus during pregnancy, and hence little is known about the role of hormonal regulation of vascular endothelial growth factor (VEGF)-receptor system expression. This study has examined the effect of insulin-like growth factor-I (IGF-I), relaxin (RLX), oxytocin (OT) and prostaglandin (PG) E(2), on VEGF secretion and VEGF-receptor system mRNA expression in the porcine endometrial stromal cells. IGF-I and RLX were identified as the most effective inducers of VEGF secretion and mRNA expression. Although PGE(2) stimulated VEGF secretion and VEGF164 mRNA expression, OT inhibited both secretion and mRNA expression of VEGF. When tested for VEGF receptors (R), all factors failed to affect their mRNA expression. Media conditioned by stromal cells collected after IGF-I and RLX treatment significantly increased endothelial cell proliferation and this effect was blocked by soluble VEGFR-1. These data suggest that during early pregnancy IGF-I, RLX and PGE(2) can affect VEGF expression in the endometrium and therefore may support uterine and embryo development, implantation and pregnancy.
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PMID:Assessment of VEGF-receptor system expression in the porcine endometrial stromal cells in response to insulin-like growth factor-I, relaxin, oxytocin and prostaglandin E2. 1856 87

In myometrium of pigs and rats, though not humans, relaxin appears to mediate an inhibition of spontaneous and oxytocin-induced contractility, presumably acting through a G-protein coupled receptor (RXFP1) to generate cAMP. In humans, circulating relaxin is highest in the first trimester, including the time of implantation, when transitory uterine quiescence could help a blastocyst to implant. We investigated whether relaxin can activate adenylate cyclase in primary human myometrial cells from non-pregnant tissue, and we show that relaxin is able to stimulate the generation of cAMP in a manner, which is dependent upon a tyrosine phosphorylation activity, as in the endometrium. We identified transcripts for the relaxin receptor RXFP1 as full-length variants, though a minor splice variant missing exon 2 was also present in low amounts. These cells also express transcripts encoding RXFP2, the receptor for the closely related hormone, INSL3. Although able to respond to relaxin at high concentrations, this receptor does not appear to function by contributing to the cAMP production in human myometrial cells, nor does INSL3 act as a functional agonist or antagonist of relaxin action. In conclusion, the inability of relaxin to inhibit contractility in human myometrial cells would appear to be due to events downstream of simple cAMP generation.
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PMID:Relaxin signalling in primary cultures of human myometrial cells. 1880 99

In pregnancy, blood volume increases greatly and plasma osmolality is reduced, due to mild hyponatraemia despite sodium retention. In rats, both vasopressin and oxytocin neurones in the supraoptic nucleus are osmosensitive and have contrasting roles in these adaptations. Increased vasopressin secretion stimulates water retention by renal actions, while oxytocin is natriuretic, partly by stimulating cardiac atrial natriuretic peptide (ANP) secretion. In pregnancy, relaxin from the corpora lutea, acting via the lamina terminalis in the presence of pregnancy levels of oestrogen and progesterone, stimulates vasopressin secretion and drinking, resulting in hypervolaemia and hyponatraemia. Initial stimulation of oxytocin secretion by relaxin is lost in late pregnancy, and oxytocin neurone responses to modest osmotic stimulation are reduced. Consequently, with reduced ANP secretion and action, sodium is retained and hypervolaemia maintained. Oxytocin neurone responses to other inputs, from hypervolaemia, immune or satiety signals, are reduced in late pregnancy by up-regulated central endogenous opioid mechanisms. Neither inhibition by opioid nor nitric oxide explains reduced responses to osmotic stimulation. Increased activity of GABA input, by allopregnanolone action, might be involved. However, the lack of a shift in threshold for hyperosmotic stimulation of oxytocin secretion in pregnancy, despite the hyponatraemia caused by relaxin, seems a sufficient explanation.
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PMID:Control of neurohypophysial hormone secretion, blood osmolality and volume in pregnancy. 1925 63


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