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)

Progesterone (P) increases PRL secretion in estrogen (E)-primed primates, but not by a direct action on lactotropes. Oxytocin is one of several hypothalamic hormones that stimulate PRL secretion. This study was conducted to determine whether oxytocin neurons directly mediate the action of P on PRL secretion. Hypothalamic sections from steroid-manipulated macaques were double immunolabeled for oxytocin and progestin receptors (PR). In addition, serum levels of oxytocin were measured in steroid-treated macaques, and hypothalamic levels of oxytocin were measured in monkeys under various physiological conditions. E treatment (28 days) of spayed monkeys caused a significant increase in the number of PR-positive neurons in the preoptic area, ventromedial nucleus, arcuate nucleus, and median eminence. Addition of P to the E treatment for the last 14 of 28 days did not change the number of PR-positive neurons in these areas. The number of PR-positive neurons was low and was unchanged by steroid treatment in the supraoptic and rostral paraventricular nuclei. Oxytocin neurons rarely contained PR regardless of anatomical location, steroid treatment, or fixation protocol. Serum oxytocin levels increased with E treatment and increased further with supplemental P treatment. The rostral and medial basal hypothalamic content of oxytocin was significantly higher in macaques with mature gonads. In conclusion, oxytocin neurons do not express nuclear PR and probably do not transcriptionally respond to P. However, gonadal steroids apparently affect the production and release of oxytocin in vivo. Thus, it is possible that oxytocin neurons transduce the action of P on PRL secretion via stimulatory neurotransmission from another PR-containing neural system.
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PMID:Search for progestin receptors (PR) in prolactin-releasing peptidergic neurons: oxytocin neurons lack PR, but respond to gonadal steroids in monkeys. 829 89

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

The effects of pregnancy, parturition and lactation and exogenous treatments with oestradiol and progesterone on oxytocin (OXY) immunoreactivity and gene expression in the sheep brain were investigated. Immunocytochemistry was used to demonstrate that increased OXY-immunoreactivity occurred in cells of the paraventricular (PVN) and supraoptic nuclei (SON), the bed nucleus of the stria terminalis (BNST), the anterior commissural nuclei (ACN) and the periventricular part of the medial preoptic area (PvMP). Oxytocin immunoreactive terminals were also seen in the accessory olfactory nucleus, the glomerular and peri-glomerular layers of the olfactory bulb, the lateral septum, the zona incerta and the pars compacta of the substantia nigra. Compared to ovariectomized and late pregnant animals, the intensity of immunoreactivity was increased in all of these oxytocinergic elements at parturition, during lactation and following exogenous treatment with oestradiol. The OXY-immunoreactivity was also more intense in late pregnant animals compared to ovariectomized ones. Quantitative in situ hybridization histochemistry showed that cells in the PVN, SON, BNST and PvMP all showed significantly increased expression of OXY mRNA in animals at parturition and during lactation compared to late pregnant or ovariectomized animals. Expression levels in late pregnant animals were also significantly higher than in ovariectomized ones. Progesterone treatment significantly increased OXY mRNA in the PVN, SON, BNST and PvMP whereas oestradiol treatment was only effective in the PVN, BNST and PvMP. Combined treatment with these steroids did not significantly increase OXY mRNA levels in comparison with their administration alone. These results show that OXY-immunoreactivity and mRNA expression are at their highest in the sheep brain when maternal behaviour is induced. The increased synthesis/storage of the peptide at parturition may be due to changes in circulating concentrations of both progesterone and oestradiol during late pregnancy.
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PMID:Changes in oxytocin immunoreactivity and mRNA expression in the sheep brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone. 840 67

Isolated porcine luteal cells from d 10 and 15 of the estrous cycle (estrus = d 0) were incubated with or without combinations of FSH (0, 10, 10(2), 10(3) ng), LH (0, 10, 10(3) ng), oxytocin, or prostaglandin F2 alpha (PGF2 alpha) (each at 0, 10, 10(3), and 10(5) pg). Progesterone (P4) content was determined after overnight incubation (0 h) then at 2 and 24 h of incubation. The basal (0 h) P4 production of large cells (LC) from d 10 corpora lutea (CL) was 31-fold higher than that by small cells (SC) at 0 h. The LC and SC from d 10 but not those from d 15, were stimulated to a small extent by LH (P < .05). The FSH inhibited P4 production (P < .05) by SC at 24 h on d 10 and by LC after 2 or 24 h of incubation on d 15. There was no interaction between LH and FSH on P4 production. Oxytocin and PGF2 alpha decreased P4 production by d 15 LC at 2 h of incubation (P < .05) and by d 15 SC after 2 or 24 h of incubation (P < .05 and P < .01). The morphology of cells from CL of the cycle or early or mid pregnancy were examined using scanning and transmission electron microscopy (EM). Freshly isolated LC (using scanning EM) from d 10 contained many microvilli arranged in apparent networks on their membranes, but SC had smooth surfaces and contained only a few microvilli. Internally, LC had more small mitochondria than did SC and a different organization of smooth endoplasmic reticulum (SER). The SC from CL of pregnant (d 30 to 60) gilts contained more mitochondria than SC from CL of cyclic gilts. The results indicate that FSH, oxytocin, and PGF2 alpha can have a direct cellular luteolytic effect in the late luteal phase in pigs. The FSH influenced LC, whereas oxytocin and PGF2 alpha effected a more pronounced decrease in P4 from SC. The lower amount of P4 produced overall by SC may be associated with fewer microvilli, mitochondria, and SER in SC.
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PMID:Responsiveness of porcine large and small luteal cells to luteotropic or luteolytic hormones and cell morphologic changes during the estrous cycle and pregnancy. 844 Jun 70

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

A study was conducted to determine the effects of pregnancy-specific protein B (PSPB) and prostaglandin F2 alpha (PGF2 alpha) on bovine luteal cell progesterone, prostaglandin E2 (PGE2) and oxytocin production in vitro. Corpora lutea were enucleated from multiparous cows with normal oestrous cycles during the mid-luteal (days 10-12; n = 5) or late-luteal (days 17-18; n = 5) stage. Mixed large and small cells (1.5 x 10(5) cells per well) were incubated in 500 microliters modified Ham's F-12 medium. Cells were incubated for 18 h before treatments were added. Cells were treated with PSPB (0, 2.5, 5.0 micrograms) and PGF2 alpha (0, 100, 200 ng) in a 3 x 3 factorial arrangement. After treatments were added, media samples were collected at 6 and 12 h. During the 18 h pretreatment incubation, progesterone, PGE2 and oxytocin production was similar between the prospective treatment groups. Progesterone production was greater (P < 0.001) by mid-stage than by late-stage cells. In addition, progesterone decreased (P < 0.001) as incubation time increased. Progesterone production was not affected by PGF2 alpha, but PSPB increased (P < 0.02) progesterone at the 5.0 micrograms dose. Late-stage luteal cells produced more (P < 0.001) PGE2 than did mid-stage cells; PGE2 production decreased (P < 0.001) with increased incubation time. Luteal PGE2 production increased in response to PSPB treatment (P < 0.01) and PGF2 alpha treatment (P < 0.001). Luteal oxytocin production was greater (P < 0.01) by mid-stage compared with late-stage cells. Oxytocin production decreased (P < 0.001) with incubation time in mid-stage cells, but in late-stage cells oxytocin production was similar over time. Neither PSPB nor PGF2 alpha had an effect on oxytocin. These results indicate that PSPB does not affect luteal oxytocin, but does increase progesterone and PGE2 production. In addition, PGF2 alpha increases luteal PGE2, but does not affect progesterone or oxytocin production. These data do not show an interaction between PSPB and PGF2 alpha in regulating bovine luteal cell endocrine function.
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PMID:Bovine luteal cell production in vitro of prostaglandin E2, oxytocin and progesterone in response to pregnancy-specific protein B and prostaglandin F2 alpha. 869 26

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

Several studies in the past few years have supported the hypothesis that oxytocin (OT) is synthesized in a paracrine system within the pregnant human uterus and that this paracrine system may be an important regulator of the timing of human parturition. Using ribonuclease protection assays, we have demonstrated a three-fold increase in the rate of synthesis of OT mRNA in human decidua around the time of parturition. We also have shown that a similar increase in OT mRNA and peptide synthesis can be stimulated in vitro by physiological concentrations of estradiol. This increase is inhibited by concomitant use of the estrogen receptor (ER) blocker tamoxifen or by transcription inhibitors. Progesterone had little, if any effect. We also detected mRNAs for ER and progesterone receptor (PR) in amnion, chorion and decidua with the same relative tissue concentrations as OT mRNA. The concentrations of ER but not PR increased significantly around the time of labour onset. To determine if local OT concentrations may be regulated by changes in OT metabolism, we determined kinetic parameters for OT metabolism in decidua, chorion and placenta. [3H]tyrosyl-OT was used as substrate. Metabolites were separated using HPLC and identified using amino acid analysis and mass spectrometry. Metabolism in decidua and chorion occurred predominantly via a cytosolic post-proline endopeptidase and the activity was comparable to placenta. In microsomal fractions, cystine aminopeptidase activity predominated and placenta had significantly more activity than decidua and chorion. There were no changes in any Km or apparent vmax values around the time of parturition. These findings support the existence of a paracrine system within human decidua that involves sex steroids regulating synthesis of OT and that undergoes significant changes around the time of parturition. Changes in local OT concentrations are controlled by rates of synthesis rather than rates of metabolism.
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PMID:Synthesis and metabolism of oxytocin in late gestation in human decidua. 871 92

Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.
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PMID:Beta-endorphin, but not oxytocin, substance P or vasoactive-intestinal polypeptide, contributes to progesterone-induced prolactin secretion in monkeys. 879 99

Three groups of intact hinds (n = 10-18) and one group of ovariectomized hinds were treated with progesterone by mean, of Controlled Internal Drug Releasing (CIDR) devices for 13 days (device removal = Day 0). Group 1 served as controls; group 2 received injections of 4 mg recombinant bovine interferon-alpha,1 twice daily from Days 13 to 21; group 3 was run with a stag from Days 0 to 3, and all hinds were subsequently diagnosed pregnant; group 4 (ovariectomized) was treated with CIDR devices and estradiol to mimic steroid secretion during the estrous cycle. Progesterone profiles were determined from thrice-weekly plasma samples from Days -13 to 28. Rectal temperature was measured in a subset of groups 1 and 2 from Days 9 to 21. Oxytocin-induced prostaglandin F2 alpha release was measured in a subset of groups 1, 2, and 4 on Days 2, 4, 10, 16, and 18. Data are presented as means +/- SEM. Exogenous interferon delayed luteolysis (> or = 28 vs. 21.2 +/- 0.55 days, P < 0.0005) and induced transient pyrexia after the first injection (39.89 +/- 0.11 vs. 38.88 +/- 0.19 degrees C, p < 0.0005). Incidence of oxytocin-induced PGF2 alpha release in control hinds was greater on Days 2 and 18 than on Days 4 and 10 (8/8 and 7/8 vs. 3/8 and 0/8, respectively; p < 0.05) and was greater in control than in interferon-treated hinds on Days 16 and 18 (5/8 and 7/8 vs. 1/8 and 1/8, respectively; p < 0.05). Profiles of plasma progesterone concentration and oxytocin sensitivity in steroid-treated ovariectomized hinds did not differ from those in control hinds. These results suggest that steroid-controlled uterine oxytocin sensitivity is important in luteolysis and is suppressed by the administration of interferon, the putative embryonic pregnancy recognition signal in red deer.
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PMID:Exogenous interferon delays luteal regression in red deer hinds (Cervus elaphus) by suppressing steroid-induced endometrial oxytocin sensitivity. 887 4


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