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)

Uterine tissue samples were collected from 47 ewes at various stages of the oestrous cycle and early pregnancy (until day 21) and during seasonal anoestrus. Cryostat sections were immunostained to determine the localization of oestradiol and progesterone receptors using specific monoclonal antibodies. Oxytocin receptors were localized by autoradiography in sections from the same ewes using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]- vasotocin. Plasma progesterone measurements were made during the preceding cycle up to the time of slaughter. Oestradiol receptor concentrations were maximal in all regions of the tract at oestrus. Immunostaining of the luminal epithelium, superficial glandular epithelium, stroma and myometrium decreased in the early luteal phase but was maintained for longer in the deep glands. Progesterone receptor immunostaining in the luminal epithelium and superficial glands developed in the early luteal phase (days 1-2) with a somewhat later appearance in the deep glands (days 5-7). Progesterone receptor concentrations in the stroma and myometrium also reached a maximum in the early luteal phase. Myometrial staining was clearly maintained throughout the luteal phase whereas stromal staining was variable between ewes. For both oestradiol and progesterone receptors no differences were apparent between pregnant and non-pregnant ewes between days 2 and 12, but pregnant ewes did not show the general increases in oestradiol receptor staining associated with luteolysis on days 14-15. Oxytocin receptors first developed in the luminal epithelium of non-pregnant ewes on day 14 of the cycle and spread to the superficial glands, caruncular stroma, deep glands and myometrium at oestrus before decreasing in reverse order on days 1-2. Specific binding was not detectable on days 5-12 of the cycle or on days 14 or 21 of pregnancy. The appearance of oxytocin receptors in the luminal epithelium on day 14 preceded that of both the oestradiol and progesterone receptors in the epithelial cells and the fall in plasma progesterone. It was followed by the development of oestradiol and oxytocin receptors in the superficial glands, deep glands, caruncular stroma and myometrium, with the two receptor populations showing a significant positive association in these tissues. The loss of oxytocin receptors in all regions occurred as plasma progesterone levels were increasing, but the association between these two variables was only significant in the superficial glands. The development of progesterone receptors in different tissues could not be explained on the basis of either oestradiol receptor content or plasma progesterone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Localization of oestradiol, progesterone and oxytocin receptors in the uterus during the oestrous cycle and early pregnancy of the ewe. 827 21

The peptide hormone oxytocin (OT) and its mRNA are synthesized by bovine granulosa cells. Bovine granulosa cells isolated before the preovulatory LH/FSH surge secrete low amounts of OT and respond to gonadotropins with an increase in OT secretion. After the LH/FSH surge, basal OT secretion increases 20-fold. At the same time, dramatic changes in steroidogenesis occur in the preovulatory follicle. Estradiol-17 beta production is high before and declines after the LH surge. The objective of this study was to determine whether steroid hormones, particularly estradiol-17 beta, influence OT secretion by bovine granulosa cells. Heifers (n = 5) were injected with prostaglandin F2 alpha (PGF2 alpha) on Day 7 of the estrous cycle to induce luteolysis. Preovulatory follicles were obtained during the ensuing follicular phase, 24 h after PGF2 alpha injection (about 24-36 h before the expected time of the preovulatory LH/FSH surge). Granulosa cells were isolated and cultured for 5 days in defined medium containing graded doses (0, 0.001, 0.01, 0.1, 1, 10 micrograms/ml) of estradiol-17 beta, testosterone, or progesterone. Media were collected daily and assayed for OT by radioimmunoassay. Addition of 0.001 or 0.01 micrograms estradiol-17 beta/ml stimulated OT secretion by granulosa cells by about 75% during the last 2 days of culture (p < 0.01). In contrast, estradiol-17 beta at high doses (1 and 10 micrograms/ml) inhibited OT secretion by 45-85% (p < 0.01). Therefore, estradiol-17 beta had a biphasic effect on OT secretion by granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estradiol-17 beta has a biphasic effect on oxytocin secretion by bovine granulosa cells. 831 93

The effects of oestradiol, progesterone, oxytocin and combinations of these hormones on oxytocin receptor binding in explants of uteri from ovariectomized ewes were determined. Receptor binding remained unchanged after 96 h in culture in control medium. Oestradiol at concentrations of 1 pmol-10 mumol l-1 did not alter receptor binding activity in tissue cultured for 96 h, but at 100 mumol l-1 oestradiol significantly reduced (P < 0.01) receptor binding activity. Progesterone and oxytocin significantly reduced receptor binding activity in explants cultured for 96 h (P < 0.05). Explants cultured in medium containing progesterone and oestradiol or oxytocin and oestradiol showed receptor binding characteristics similar to those found in tissue cultured with progesterone or oxytocin alone. When explants were cultured for 72 h in medium containing oestradiol followed by 24 h in medium containing oestradiol alone, oestradiol with oxytocin, oestradiol with progesterone, oxytocin alone, progesterone alone, or in medium with no added hormones, receptor binding activity was always reduced in the presence of progesterone and oxytocin whether or not oestradiol was present in the medium. Receptor binding activity in explants cultured for the final 24 h in medium containing oestradiol or no added hormones were similar to those in tissue cultured in control medium for a total of 96 h. These data show that progesterone and oxytocin reduce oxytocin receptor binding activity in cultured uterine tissue and, in contrast to its effect on the rat uterus, that oestradiol is not a potent stimulator of oxytocin receptor synthesis in uterine tissue of ovariectomized ewes in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ovarian hormones on oxytocin receptor concentrations in explants of uterus from ovariectomized ewes. 838 22

Despite the widespread clinical use of oxytocin (OT) as a potent and specific stimulant of labor, previous research data have not supported a role for OT in the physiology of normal human parturition. We have demonstrated synthesis of OT mRNA in amnion, chorion, and decidua using Northern blot analysis, ribonuclease protection assays, and in situ hybridization. Probes directed towards both the 3' and 5' ends of the gene have been used. Levels were highest in decidua with considerably less in chorion and amnion and very low levels in placenta. The transcript size in decidua appears to be 60-80 nucleotides smaller than the transcripts in amnion and chorion. OT gene expression in chorio-decidual tissues increased three- to fourfold around the time of labor onset. Estradiol stimulated synthesis of OT mRNA during in vitro incubation. These results support the hypothesis of a paracrine system involving OT and sex steroids within intrauterine tissues wherein significant changes could occur without being reflected in the maternal circulation. Such a paracrine system could rationalize a long-sought role for oxytocin in the physiology of human labor. These data may lead to novel approaches towards prevention or treatment or preterm labor.
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PMID:Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition. 842 17

We have studied oxytocin (OT) gene expression, secretion, and action in bovine preovulatory follicles during the follicular phase of the estrous cycle. OT is secreted in vitro by follicular granulosa cells, but not by theca cells. Both OT content of granulosa cells and their ability to secrete OT in culture increased dramatically when follicles were obtained after the gonadotropin surge (LH surge) that triggers ovulation. These changes were correlated with increased levels of messenger RNA (mRNA) for OT in granulosa cells obtained after vs. before the LH surge. When granulosa cells were obtained before the surge, both OT secretion and OT mRNA levels increased with time in culture, and the increases were greatly enhanced in the presence of LH. Estradiol, at concentrations found in follicular fluid of preovulatory follicles before the LH surge, inhibited OT secretion in vitro, whereas concentrations found in follicular fluid after the LH surge were not inhibitory. Progesterone, at physiological concentrations, stimulated OT secretion in vitro. We have shown previously that OT increases progesterone secretion by granulosa cells obtained before the LH surge. Taken together these results show that, during the follicular phase in cattle, OT secretion and gene expression are coordinately regulated and suggest that they are regulated by both gonadotropins and intrafollicular steroids. Increases in OT after the LH surge may play a role in the follicular/luteal phase shift in steroidogenesis from estradiol/androgen to progesterone.
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PMID:Oxytocin gene expression and action in bovine preovulatory follicles. 851 53

In the female sheep opioids act centrally to influence both oxytocin release and maternal behaviour. We have used in situ hybridization and histochemistry to investigate the changes in mRNA expression of the two opioid precursor genes, pro-opiomelanocortin (POMC) and pre-proenkephalin (PPE), in discrete hypothalamic nuclei as a function of pregnancy, parturition and lactation and following treatment with oestrogen and progesterone. Quantitative in situ hybridization histochemistry demonstrated that POMC mRNA expression in the arcuate nucleus (ARC) decreased at parturition and increased during lactation compared to late pregnant and ovariectomized animals. Oestradiol and progesterone treatments increased POMC mRNA expression compared to ovariectomized controls. Pre-proenkephalin mRNA expression was quantified in three discrete hypothalamic nuclei, the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the suprachiasmatic nucleus (SCN). In the VMN, PPE mRNA expression increased during lactation compared to late pregnancy and parturition. Expression levels during late pregnancy and parturition were decreased compared to ovariectomized animals. Oestradiol increased, and progesterone decreased, PPE mRNA levels compared to ovariectomized controls. Combined progesterone followed by oestrogen treatment produced significant increases in PPE mRNA expression. In the PVN, PPE expression increased at parturition compared to late pregnant, lactating and ovariectomized animals. Expression levels in late pregnant animals were decreased compared to lactating or ovariectomized ones. However, sex steroid treatment produced no changes in PPE expression in the PVN. No changes were observed in PPE mRNA expression in the SCN in response to any of the experimental conditions. This data shows that both POMC and PPE mRNA levels are altered in the sheep brain during pregnancy, parturition and lactation and in response to sex steroids, although the direction of the changes is not always the same and in the case of PPE only the VMN and PVN are affected.
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PMID:Changes in pro-opiomelanocortin and pre-proenkephalin mRNA levels in the ovine brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone. 868 Apr 46

In the rat, the synchronous bursting activity of oxytocin neurones associated with the milk-ejection reflex displays important changes during the peri-partum and lactational periods. The most dramatic of these changes is the appearance of a facilitatory response to centrally-administered oxytocin, involving an increase in the frequency and amplitude of bursting in the oxytocin neurones, as well as elevation of their background activity. Studies of rats at different times in the pre- and post-partum period show that this response first appears on day 3 of lactation. Ovariectomy on day 21 of gestation, or treatment with the anti-oestrogen tamoxifen on day 22, does not prevent the appearance of this response. However, ovariectomy and treatment with ovarian steroids for 3 days prior to parturition can dramatically alter the character of the facilitatory response. Oestradiol treatment causes an early (pre-partum) appearance of the facilitatory response, whereas progesterone causes the appearance of an inhibitory response (reduction in milk-ejection frequency) to central oxytocin. A major target for the central effects of oxytocin are the bed nuclei of the stria terminalis (BST) and modulation of the neuronal responses in this region may, in part, underlie the changing facilitatory effects. In vitro recordings indicate that sensitivity of BST neurones to oxytocin is increased between pregnancy and lactation, and oestradiol treatment enhances responsiveness coincident with the appearance of a facilitatory response. Progesterone pre-treatment also increases the ability of BST neurones to respond to oxytocin in vitro (although less than oestradiol), an unexpected result given the absence of oxytocin-induced facilitation of the milk-ejection reflex in late pregnancy or following progesterone treatment in vivo. In vivo recordings of BST neurones suggest that one explanation of this lack of correlation may reside in the presence of a mechanism which attenuates the excitatory response to oxytocin, perhaps serving to prevent premature expression of the facilitatory action of oxytocin. Collectively, these data show that there are dramatic reproductive state and steroid-dependent changes in the central action of oxytocin on the synchronous bursting of magnocellular oxytocin neurones. These changes, which have important consequences for the optimization of bursting in oxytocin neurones, may involve plasticity of transduction mechanisms in the oxytocin-responsive elements of the limbic system.
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PMID:Influence of reproductive state and ovarian steroids on facilitation of the milk-ejection reflex by central oxytocin. 871 59

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

The aim of this study was to measure oxytocin receptor concentration in myometrial tissue from term pregnant women with normal and dysfunctional labor and to relate this concentration to the progress of labor and to the levels of estradiol and progesterone in the same myometrium. Myometrial biopsies were obtained from 50 term pregnant women undergoing cesarean section. The patients were categorized as follows: not in labor, normal labor, successful oxytocin-augmented labor, and oxytocin-resistant labor. Specific binding of [3H]oxytocin to high-affinity sites in membrane preparations from myometrial tissues was determined. Estradiol and progesterone were assayed using tritiated steroids with a sensitive radioimmunoassay technique. Oxytocin receptor density was significantly lower in oxytocin-resistant labor compared to successful oxytocin-augmentated labor (P < 0.04) and to spontaneously active normal labor (P < 0.02). Oxytocin receptor concentration was also significantly lower in non-labor patients compared to normal spontaneous labor (P < 0.01), and successful oxytocin-augmented labor (P < 0.02). There was a positive relationship between the progress of cervical dilatation (cm/h) and oxytocin receptor density in the myometrium (r = 0.408, P < 0.025). The concentration of progesterone and estradiol in the pregnant myometrium did not differ in patients with different types of labor or with the state of uterine contractile activity. Our results suggest that individual myometrial sensitivity is an important determinant of the response to administered oxytocin in humans. Furthermore, myometrial oxytocin receptor expression in vivo seems not be related to ovarian steroid concentration in the myometrium. The low oxytocin receptor density in oxytocin-resistant dystocia needs further investigation.
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PMID:Myometrial steroid concentration and oxytocin receptor density in parturient women at term. 877 95

The aim of the present experiments was to demonstrate the release of insulin-like growth factor-I (IGF-I) by human granulosa cells, and to examine the role of growth hormone (GH), oxytocin, steroids and cAMP-dependent intracellular mechanism in its control. A significant accumulation of IGF-I in a serum-supplemented medium in which the human granulosa cells were cultured for 4 days was observed. The concentration of IGF-I in the medium was particularly high at 3 and 4 days of culture. The addition of GH (1-10,000 ng/ml) to the medium increased IGF-I secretion by the cells. A higher GH dose (100,000 ng/ml) was inhibitory. Oxytocin stimulated IGF-I release at doses of 10-10,000 ng/ml. Dibutyryl-cAMP, isobutyl-methyl-xanthine (inhibitor of cAMP catabolism) or forskolin (stimulator of cAMP production) inhibited IGF-I output at these doses. Additions of progesterone (1-1,000 ng/ml) did not affect IGF-I release, whilst adrostenedione and estradiol were stimulatory at doses of 1, 10, 100, 1,000 ng/ml and 10, 100 and 1,000 ng/ml respectively. Testosterone inhibited IGF-I at a dose of 1,000 ng/ml but not at lower doses (1, 10 or 100 ng/ml). Blockade of estradiol (but not of testosterone) in the medium by specific antisera (1 or 10%) significantly reduced IGF-I output. The same effect was observed with an antiserum to progesterone when added at 0.1%, whilst higher doses (1 or 10%) stimulated IGF-I secretion. The present observations demonstrate the involvement of peptide, steroid hormones and cAMP in the regulation of IGF-I secretion by luteinized human granulosa cells. In particular, both GH and oxytocin are stimulators of IGF-I release. Estradiol and androstenedione, but not testosterone, may also be stimulators of IGF-I output. The involvement of progesterone in this process can also not be excluded. A cAMP-dependent intracellular mechanism appears to play an inhibitory role in the regulation of IGF-I secretion by luteinized human granulosa cells.
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PMID:The release of insulin-like growth factor-I by luteinized human granulosa cells in vitro: regulation by growth hormone, oxytocin, steroids and cAMP-dependent intracellular mechanisms. 878 8


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