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)

The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.
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PMID:Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol. 650 64

The effect of oxytocin on collagen metabolism in the cervix and lower uterine segment of pregnant women was studied by measuring the incorporation of [3H]proline in vitro. Oxytocin had a concentration related inhibitory effect on the labelling with [3H]proline. Addition of indomethacin did not influence the response to oxytocin indicating that the effect was not directly mediated by prostaglandins. Oestradiol-17 beta potentiated the effect of oxytocin. Vasopressin decreased the incorporation of [3H]proline slightly but the action of this hormone was significantly less than that of oxytocin. The results suggest that oxytocin under in vitro experimental conditions influences cervical connective tissue metabolism which is in contrast to current clinical experiences.
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PMID:Effects of oxytocin on cervical and uterine connective tissue. 673 Aug 60

Agents influencing the output of prostaglandin F2 alpha (PGF2 alpha) from non-pregnant endometrium were investigated by in vitro incubation, for 5 and 19h, using mid-cycle (day 7), end of cycle (day 15), or ovariectomised guinea-pigs. Estradiol 17-beta (10 micrograms/ml) stimulated PGF2 alpha output 24h after incubation with endometrium (p less than 0.05). This stimulation was greater at mid-cycle. Progesterone (50 ng/ml) inhibited output of PGF2 alpha (p less than 0.05) in mid-cycle, end of cycle and ovariectomised guinea-pig cultures. Oxytocin (1 X 10(-5) u/ml) stimulated the output of PGF2 alpha at the end of the cycle, but not at mid-cycle. However, in the presence of estradiol 17-beta (10 micrograms/ml), oxytocin stimulation of mid-cycle PGF2 alpha output was observed. The calcium ionophore A23187 (5 micrograms/ml) stimulated PGF2 alpha synthesis from mid-cycle and end-of-cycle endometrium, and this stimulation resembled that caused by arachidonic acid (100 micrograms/ml), suggesting an action via substrate mobilisation. Co-culture of endometrium and myometrium did not influence endometrial PGF2 alpha or myometrial 6-oxo-PGF2 output. It is suggested that the steroid hormones act as coarse modulators of endometrial PGF2 alpha output, but more rapid changes may be achieved by oxytocin and agents that mobilise substrate supply, possibly via calcium ion fluctuations.
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PMID:Control of endometrial prostaglandin output in vitro during the estrous cycle of the guinea-pig: influence of estradiol 17-beta, progesterone, oxytocin and calcium ionophore A23187. 681 62

In order to elucidate the mechanism of prostaglandin F2 alpha (PGF2 alpha) action to onset of labor, the author observed the changes in maternal peripheral plasma oxytocin, progesterone, estradiol and cystine-aminopeptidase (CAP) activity around the onset of labor by PGF2 alpha. For the investigation, 66 normal pregnant women from 6 to 10 gestational months and same numbers from 39 to 41 gestational weeks were chosen. The blood samples for the latter were drawn just before drip infusion of PGF2 alpha, 5-minutes interval, 3-minutes interval of pain and just after labor. PGF2 alpha administered for labor induction intravenously, and 55 pregnant delivered. 1) The maternal peripheral mean plasma concentrations of them showed increase during pregnancy. There were positive correlations between oxytocin and progesterone, estradiol, CAP. 2) During labor, oxytocin levels increased significantly (p less than 0.01) and progesterone levels decreased significantly (p less than 0.01). On the other hand estradiol levels did not change significantly. CAP levels showed irregular changes. Estradiol-progesterone ratio showed gradual increase. 3) Then during labor, progesterone levels showed negative correlation with oxytocin levels. From this study, the results indicate that significant changes in oxytocin and progesterone and gradual increase estradiol-progesterone ratio are concerned in the onset of labor caused by PGF2 alpha, so labor may progress dynamically.
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PMID:[Changes of oxytocin, progesterone, estradiol and CAP around the labor by prostaglandin F2 alpha (author's transl)]. 694 20

To determine if oxytocin and estradiol were effected by pelvic neurectomy (PN), utero-ovarian vein blood was collected from PN rats during the preparturient period and assayed for these hormones. Radioimmunoassayable oxytocin levels were not significantly different in any groups of sham operated (S) or PN animals on days 21 and 22 or PN animals on days 23 and 24. Estradiol (E2) levels rose significantly on day 22 in S animals but there was no significant change in E2 in PN rats throughout the time period studied, although E2 levels were generally high. These results indicate that the blocked parturition characteristic of PN animals cannot be attributed to altered oxytocin levels. The lack of a significant E2 surge on day 22 in PN rats may contribute to the failure of utero-ovarian vein prostaglandin F levels to rise in these animals during the preparturient period.
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PMID:Plasma oxytocin and estradiol in pelvic neurectomized rats with blocked parturition. 712 50

Oestradiol acting on a progesterone-primed uterus stimulates prostaglandin (PG) F2 alpha synthesis by the endometrium. In some species (notably the sheep, cow and goat) oxytocin released from the ovary also forms part of the physiological stimulus for increased endometrial PGF2 alpha production. The corpus luteum contains high concentrations (> 1 microgram/g tissue) of this peptide in these species. The intracellular mechanisms by which these three hormones control endometrial PGF2 alpha synthesis and release are far from clear. Oxytocin stimulates the synthesis of inositol phosphates and diacylglycerol in the endometrium of some species, but whether this pathway is involved in endometrial PGF2 alpha synthesis is still open to question. There is evidence that increased endometrial PGF2 alpha synthesis is dependent upon increased endometrial protein synthesis but, apart from the recorded effects of steroid hormones on the concentrations of phospholipase A2, prostaglandin H synthase and oxytocin receptors, it is not known what other endometrial proteins are involved. Some disorders of menstruation are associated with abnormal PG production by the endometrium, but the reasons for this abnormality are not clear. During early pregnancy an increase in PGF2 alpha synthesis by the endometrium is prevented, except in the pig where the PGF2 alpha produced is directed from the venous drainage to the uterine lumen. In those species in which endometrial PGF2 alpha synthesis is dependent upon oxytocin secreted by the ovary, the conceptus secretes an interferon-tau (previously named trophoblast protein-1) which prevents oestradiol and oxytocin acting on a progesterone-primed uterus from stimulating endometrial PGF2 alpha synthesis. The identities of the factors produced by the conceptus which prevent endometrial PGF2 alpha synthesis during early pregnancy in other species are not known, although it is clear that they are not interferons.
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PMID:The control of prostaglandin production by the endometrium in relation to luteolysis and menstruation. 748 81

It is not known whether the equine preovulatory follicle produces oxytocin or is a target tissue for oxytocin, as has been reported for other species, especially ruminants. Bovine granulosa cells secrete oxytocin, and oxytocin modulates the production of progesterone by granulosa cells in vitro. We examined whether oxytocin plays a comparable role in the equine preovulatory follicle. To test the hypothesis that the equine preovulatory follicle produces oxytocin during estrus and that its production increases in late estrus, preovulatory follicles were isolated during early (Days 1 to 2; n = 4) and late (Days 4 to 5; n = 4) estrus. Granulosa cells, pieces of theca interna and pieces of follicle wall (theca with attached granulosa cells) were cultured for 3 d with or without equine gonadotropins. Culture media were collected, replaced at 3, 6, 12, 24, 48, and 72 hr of culture, and assayed for oxytocin. Granulosa cells from preovulatory follicles secreted negligible amounts of oxytocin during 3 d of culture, irrespective of gonadotropin treatment or stage of estrus. Likewise, negligible amounts of oxytocin were measured in theca and follicle wall cultures at both developmental stages, in the presence or absence of gonadotropins. Furthermore, follicular fluid from early or late estrous follicles contained only negligible amounts of oxytocin. To determine if oxytocin affects steroidogenesis by equine granulosa cells, granulosa cells from follicles obtained on Day 2 of estrus were cultured with graded doses of oxytocin (0, 1, 10, 100, and 1,000 ng/ml) in defined medium supplemented with testosterone (0.5 microM) and culture media were assayed for estradiol-17 beta and progesterone. Estradiol was secreted throughout the culture period, and its production was not significantly affected by oxytocin treatment (P > 0.05). Progesterone secretion was relatively low during the first 24 hr of culture, increased dramatically on the second day of culture, and remained high through the third day. No dose of oxytocin had a significant effect on progesterone secretion (P > 0.05). In conclusion, the results indicate that equine preovulatory follicles, isolated during early or late estrus, are neither a source of oxytocin nor a target for oxytocin action on steroidogenesis. Although ovarian oxytocin appears to play a role in regulating follicular function in some other mammalian species, our data provide no support for such a role for oxytocin in mares.
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PMID:Oxytocin in mares: lack of evidence for oxytocin production by or action on preovulatory follicles. 760 Jul 64

Neuroactive steroid modulation of GABAA receptors was investigated in the peptidergic nerve terminals of the posterior pituitary using patch clamp techniques. In common with GABAA receptors in cell bodies, the nerve terminal GABAA receptor was potentiated by the synthetic steroid alphaxalone and by physiological concentrations of the progesterone metabolite allopregnanolone. Both of these agents enhanced Cl- currents elicited by GABA. Estradiol-17 beta had a weak inhibitory effect on GABA responses of nerve terminals, but only at high concentrations. The potentiating action was manifest as an increase in the probability of channel opening, with no effect on the rate of desensitization of the GABAA receptor. Neuroactive steroids enhanced GABA-gated Cl- channel activity in cell-free membrane patches, thus demonstrating a membrane delimited response. These results indicated that with regard to allosteric modulation by neuroactive steroids, the nerve terminal GABAA receptor is similar to the GABAA receptors of nerve cell bodies and endocrine cells. Neuroactive steroids are thus capable of altering the chemosensitivity of nerve terminal membranes by enhancing GABA inhibition at this location. The neuroactive steroid sensitivity of nerve terminal GABAA receptors provides a pathway by which gonadal steroid derivatives could regulate peptide secretion from neurosecretory neurons. Such a pathway could participate in the coordination of neuropeptide secretion during complex neuroendocrine functions. With specific regard to the neurohypophysis, neuroactive steroid-induced changes in the sensitivity of nerve terminal GABAA receptors could play a role in the initiation of oxytocin secretion during the transition between pregnancy and parturition.
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PMID:Neuroactive steroids modulate GABAA receptors in peptidergic nerve terminals. 782 23

Human myometrium contains hCG/LH receptors. There are fewer of these receptors during labor compared to no labor at preterm or term deliveries. Exogenous hCG can directly inhibit oxytocin-stimulated human myometrial contractions. These findings suggest that hCG may directly maintain myometrial quiescence during pregnancy. As maintenance of uterine quiescence may involve down-regulation of myometrial gap junctions, we investigated the effect of hCG on connexin-43 (CX-43) gene expression from RNA to protein and morphological gap junctions. The addition of 5 or 10 nM highly purified hCG to subconfluent cultures of pregnant myometrial smooth muscle cells resulted in a significant decrease in CX-43 protein levels. Higher hCG concentrations (100 and 1000 nM), however, had no effect. The maximal effect of hCG was seen at 4-8 h of culture, followed by recovery after a longer duration of culture. hCG treatment also concomitantly decreased CX-43 messenger RNA and morphological gap junctions. The hCG effect on CX-43 protein levels is hormone specific and mediated by protein kinase-A signaling. Estradiol and oxytocin increased, whereas progesterone decreased, CX-43 protein levels and morphological gap junctions. The oxytocin-induced increase was reversed by cotreatment with hCG. Although RU 486 alone had no effect on CX-43 protein levels, it prevented the down-regulating action of hCG and progesterone. In summary, our results demonstrate that hCG can directly decrease CX-43 messenger RNA, protein, and morphological gap junctions in cultured pregnant human myometrial smooth muscle cells. The hCG action is concentration and time dependent, hormone specific, and mediated by protein kinase-A signaling and appears to involve progesterone receptors. These data lend support to the concept that hCG could be one of the hormones responsible for maintaining uterine quiescence by down-regulating myometrial gap junctions during pregnancy.
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PMID:Novel regulation of pregnant human myometrial smooth muscle cell gap junctions by human chorionic gonadotropin. 798 70

Previous reports have suggested that gonadotropins, estradiol, and prostaglandin F2 alpha (PGF2 alpha) have varying effects on progesterone and oxytocin synthesis or secretion in cultured granulosa and luteal cells collected at different stages of the estrous cycle. The experiments reported here were designed to investigate whether effects of these agonists on secretion of hormones and their coupling to second messenger systems changed around the time of ovulation. Granulosa cells and Day 2 luteal cells of the ewe were cultured for three days and then treated for 30 min with varying doses of PGF2 alpha, LH, or estradiol. LH increased intracellular cAMP at both stages, but granulosa cells were more responsive in terms of both minimum effective dose (10 compared with 100 ng/ml) and degree of stimulation. LH caused no change in intracellular inositol phosphate levels. Both granulosa and early luteal cells responded to LH treatment by an increase in progesterone output in a dose-responsive fashion. PGF2 alpha increased inositol phosphate accumulation in cells collected at both stages of the cycle. All doses tested (10(-6)-10(-8) M) stimulated the release of oxytocin into the culture medium from both granulosa and luteal cells. Progesterone secretion was also increased, but only at the highest dose (10(-6) M). Estradiol treatment (10(-6) M) did not affect either the inositol phosphate or cAMP second messenger systems, but it did inhibit the secretion of oxytocin from granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute effects of prostaglandin F2 alpha, luteinizing hormone, and estradiol on second messenger systems and on the secretion of oxytocin and progesterone from granulosa and early luteal cells of the ewe. 819 57


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