Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using in situ hybridization methods that discriminate mRNAs encoding rat vasopressin V1a, V1b, V2 and oxytocin receptors in hepatic, brain and renal tissues, experiments were done to determine whether estrogen and/or progesterone influence renal vasopressin receptor (VR) or oxytocin receptor (OTR) transcripts. Estrogen induced OTR gene expression in the outer stripe of the outer medulla and increased expression of OTRs in macula densa cells. Outer stripe OTR mRNA peaked with 4 days of estrogen treatment, and decreased to undetectable levels with 31 days of treatment of ovariectomized females. Estradiol's induction of outer stripe OTR mRNA expression was blocked by the antiestrogen, tamoxifen, but was not affected by high levels of circulating oxytocin. A role for OTRs in regulating renal function independently of adrenal steroids was suggested by findings that adrenalectomized males showed high levels of OTR transcripts in outer stripe proximal tubule and cortical macula densa cells after 5 and 10 micrograms/100g of estradiol. Consistent with specialized roles for OTRs during female reproduction, OTR transcripts could not be detected in renal tissues of peri-parturient females, at times when OTR mRNA levels were very high in uterus. OTR gene expression in macula densa cells reappeared 4-8 days into lactation and attained control levels by day 20. Physiological experiments showed that estrogen + oxytocin decreased plasma [Na+] levels in ovariectomized rats at a time when proximal tubule OTR expression is maximal. These data are consistent with 1) cell-specific regulation by estrogen of renal OTR gene expression and 2) the possibility that OTRs may be important mediators of steroid-induced alterations in renal fluid and/or solute reabsorption.
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PMID:Oxytocin receptor gene expression in female rat kidney. The effect of estrogen. 871 83

Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and (35)S-labeled in vitro translated RXR constructs confirmed binding of delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements.
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PMID:Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor. 909 98

Parturition is a multifactorial physiological process that involves multiple interconnected positive feedforward and negative feedback loops. Each of these loops is connected to others in a carefully time-regulated fashion. When parturition occurs normally, both fetal and maternal processes are involved. Recent research in pregnant sheep and nonhuman primates shows clearly that the fetus determines the duration of gestation and the mother determines the time of day at which labor begins. The fetal hypothalamo-pituitary-adrenal axis plays a fundamental role in stimulating increased estrogen production in late gestation. Estrogen then activates maternal circadian rhythms that increase oxytocin secretion. As a result, uterine contraction patterns are switched from contractures to contractions.
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PMID:Comparative studies on the initiation of labor. 962 9

The objective of the present study was to further elucidate our previous observation that beta2-adrenoceptor activation induces oxytocin receptor (OTR) expression in rat myometrium. We wanted to investigate whether the mechanism behind this effect was under the influence of gonadal steroids. Ovariectomized non-pregnant rats were treated with estrogen, progesterone or a combination of both for 3 days. Some rats were concomitantly treated with isoproterenol. Estrogen treatment increased both OTR mRNA production and maximal binding of [3H]-oxytocin to isolated myometrial plasma membranes, but it did not affect contractility of isolated uterine strips challenged with oxytocin. When the estrogen regimen was combined with isoproterenol treatment, an augmented maximal contractile response (Emax) to oxytocin was observed although no further increase in OTR mRNA and binding was seen. Progesterone treatment did not in itself alter OTR mRNA, OTR binding or Emax. However, OTRs were induced at the level of gene expression when progesterone was supplemented with isoproterenol infusion. Finally, progesterone suppressed the effect of estrogen on OTR mRNA production and binding when the two compounds were administered together. However, when isoproterenol treatment was added this effect was abolished and Emax was enhanced more than that seen following treatment with estrogen alone. These data suggest that beta2-adrenoceptor activation represents an important regulator of OTR expression/function in estrogen- and progesterone-dominated rat myometrium.
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PMID:Up-regulation of oxytocin receptors in non-pregnant rat myometrium by isoproterenol: effects of steroids. 1033 43

Marked plasticity in GABAA receptor signalling occurs in adult oxytocin neurons of the supraoptic nucleus (SON) through the modulation of GABAA receptor alpha subunits during pregnancy. The present studies were undertaken to examine the potential mechanisms underlying this plasticity. In vivo microdialysis experiments in conscious rats revealed that no significant changes in extracellular GABA concentrations occurred within the SON over the last two days of pregnancy and the time of parturition itself. In situ hybridization studies examined the effects of gonadal steroid manipulation upon the GABAA receptor subunits expressed by SON neurons (alpha1, alpha2, beta2 and gamma2 subunits) and demonstrated that cellular levels of the alpha1 subunit were increased following 8 days oestrogen and progesterone treatment. Estrogen alone or allopregnanolone, the progesterone derivative, had no effect on alpha1 subunit mRNA expression in the SON. Immunocytochemical experiments demonstrated progesterone receptors in many neural populations but not within the SON of late pregnant rats. These studies indicate that alterations in endogenous GABA release within the SON are unlikely to be responsible for the GABAA receptor plasticity exhibited by oxytocin neurons in late pregnancy. Rather, data demonstrate that the fluctuating concentrations of progesterone during pregnancy act indirectly on SON neurons to modulate alpha1 subunit mRNA expression. Together, these experiments provide evidence for the ligand-independent induction of GABAA receptor plasticity in the adult brain by progesterone.
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PMID:Progesterone regulation of GABAA receptor plasticity in adult rat supraoptic nucleus. 1079 39

Estrogen-regulated gene expression is dependent on interaction of the estrogen receptor (ER) with the estrogen response element (ERE). We assessed the ability of the ER to activate transcription of reporter plasmids containing either the consensus vitellogenin A2 ERE or the imperfect pS2, vitellogenin B1, or oxytocin (OT) ERE. The A2 ERE was the most potent activator of transcription. The OT ERE was significantly more effective in activating transcription than either the pS2 or B1 ERE. In deoxyribonuclease I (DNase I) footprinting experiments, MCF-7 proteins protected A2 and OT EREs more effectively than the pS2 and B1 EREs. Limited protease digestion of the A2, pS2, B1, or OT ERE-bound receptor with V8 protease or proteinase K produced distinct cleavage products demonstrating that individual ERE sequences induce specific changes in ER conformation. Receptor interaction domains of glucocorticoid receptor interacting protein 1 and steroid receptor coactivator 1 bound effectively to the A2, pS2, B1, and OT ERE-bound receptor and significantly stabilized the receptor-DNA interaction. Similar levels of the full-length p160 protein amplified in breast cancer 1 were recruited from HeLa nuclear extracts by the A2, pS2, B1, and OT ERE-bound receptors. In contrast, significantly less transcriptional intermediary factor 2 was recruited by the B1 ERE-bound receptor than by the A2 ERE-bound receptor. These studies suggest that allosteric modulation of ER conformation by individual ERE sequences influences the recruitment of specific coactivator proteins and leads to differential expression of genes containing divergent ERE sequences.
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PMID:Allosteric modulation of estrogen receptor conformation by different estrogen response elements. 1143 12

This review of the physiology of ovarian contractility cites the functions of FSH and LH and the contribution of chorionic gonadotropin (HCG) to follicular swelling and rupture. Endogenous estrogen priming seems to be needed for this response. Luteninizing hormone releasing hormone (LHRH) administered during the ovulatory phase also causes changes to occur in ovaries treated with smooth muscle stimulants. A contractile response may be induced by alpha-adrenergic receptors, which confirms the finding of smooth muscle fibers in the ovaries. Spontaneous contractions have also been observed in ovaries removed from animals at estrus. Estrogen activate, progesterone inhibits ovarian contractility. In rabbits and guinea pigs spontaneous activity of the ovary is increased during early pregnancy. Treatment with nor- epinephrine inhibits this. Quiescent ovaries show marked activation with nor-adrenergic compounds such as nor-epinephrine and phenilephrine. Pretreatment with alpha-adrenergic blocking agents such as progranolol reverses this effect. Prostaglandin F-2-alpha is a more powerful stimulant on ovarian motility than vasopressin or oxytocin. The role of ovarian contractions in the reproductive function is still unknown. Further studies may provide ways of interfering with reproduction at the ovarian level.
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PMID:Ovarian contractility and ovulation. 1225 6

The impact of colitis on uterine contractility and estrous cycle was investigated after intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Colitis severity was assessed by macroscopic damage scoring (MDS) 4 days after TNBS, and myeloperoxidase (MPO) activity was measured in both colon and uterus of control and colitic rats. Estrous cycle stages were determined by vaginal smears and histology, and uterine contractility was assessed in vitro on longitudinal and circular strips. In control rats, uterine MPO activity varied markedly during the cycle and peaked around estrus. In rats with moderate colitis [MDS < 5, 3.1 +/- 0.2 (mean +/- SE)], uterine MPO decreased by 61% compared with estrus control, without disruption of the cycle. Frequency of spontaneous contractions was reduced by 32% in circular muscle. Contractile responses to KCl and carbachol were not affected, whereas maximal response to oxytocin decreased by 47% in the longitudinal muscle. In rats with severe colitis (MDS > 5, 6.0 +/- 0.2), uterine MPO was reduced by 96% and estrous cycle was disrupted. Spontaneous contractility was impaired in circular strips, and a 39% decrease in the contraction frequency occurred in the longitudinal strips. Circular strips did not contract to KCl or carbachol; however, longitudinal strips had maximal responses to KCl, carbachol, and oxytocin reduced by 36%, 27%, and 46%, respectively. Estrogen replacement protected the uterine responses to carbachol in colitic rats, whereas oxytocin responses remained depressed. These data indicate that colonic inflammation can influence both spontaneous and evoked uterine contractility, in relation to estrous cycle disturbances, impaired estradiol production, and functional alterations of myometrial cells.
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PMID:Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat. 1553 8

Estrogen administration results in increased release of the oxytocin (OT) prohormone reflected by increases in oxytocin intermediate peptide (OT Int) in both animal models and humans, and sequential treatment of ovariectomized rats with estrogen/progesterone then progesterone withdrawal leads to increased hypothalamic OT mRNA. Blood pressure (BP) reductions have been related to increased exogenous and endogenous OT in rats and to higher endogenous OT activity in premenopausal women, but not previously in postmenopausal women. Thus, we used plasma obtained at rest and during a speech stressor from 54 postmenopausal women who participated in a 6-month randomized trial of oral conjugated estrogens vs. placebo to examine effects of estrogen replacement therapy (ERT) on plasma OT and OT Int levels and their relationships to changes in BP during the trial. ERT alone and with progesterone (but not placebo) led to significant increases in plasma levels of OT Int, but no change in plasma OT levels. Women showing greater increases in OT Int during treatment showed greater decreases in BP and total vascular resistance during a series of behavioral stressors compared to women with moderate or no increases in OT Int, even after controlling for effects related to treatment condition or to changes in plasma estradiol. The findings suggest that enhanced oxytocinergic activity may contribute to BP decreases associated with ERT in more responsive postmenopausal women.
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PMID:Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement. 1581 55

Adequate uterine contractility and periovulatory peristalsis, interpreted as "rapid sperm transport" to the side bearing the dominant follicle, may be a precondition for successful reproduction in humans. Estrogen and progesterone fluctuate characteristically during the menstrual cycle, and their source is the dominant follicle and corpus luteum. The question is, how is the direction to the left or right side of transport mechanisms influenced? An extracorporeal perfusion model of the swine uterus was used that maintained the uterus in a functional condition and that was suitable for the study of physiological questions. The effects of side-dependent estrogen, progesterone, and estrogen plus progesterone perfusion on oxytocin-induced uterine peristalsis were assessed using two intrauterine microcatheters placed in each horn of the swine uterus. Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner only in the estrogen-perfused horn of the swine uterus. There was a significant difference between the IUP increase measured in the estrogen-perfused horn and that in the non estrogen-perfused horn of the swine uterus. Progesterone perfusion showed no effect in general. Furthermore, progesterone antagonized the estrogen effects. This study demonstrates that side-dependent estrogen perfusion resulted in side-dependent contractility in the swine uterus perfusion system used. These observations show that estrogen stimulates uterine contractility in the estrogen-perfused uterine horn and that estrogens may be the "trigger" for the transport mechanisms to the side bearing the dominant follicle during the periovulatory phase through their locally increased concentration and distribution via the utero-ovarian counter-current system in humans.
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PMID:Perfused non-pregnant swine uteri: a model for evaluating transport mechanisms to the side bearing the dominant follicle in humans. 1681 58


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