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

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

Estradiol conjugated to bovine serum albumin at position 6(E-6-BSA) released oxytocin (OT) from homogenates of the medial preoptic area and medial hypothalamus (MPOA-MH) within minutes of its superfusion. Using a superfusion system in which synaptosome-containing homogenates were layered onto acrodiscs maintained at 37 degrees C, we have found that E-6-BSA (100 ng/microliters) superfusions significantly elevated OT release within minutes. In contrast, superfusion of the same concentration of BSA or progesterone-3-BSA (P-3-BSA) had no effect on OT release. While superfusing homogenates with augmented levels of K+ had no effect on OT release itself, superfusing E-6-BSA with these concentrations of K+ consistently increased OT release. This is the first demonstration that E-6-BSA increases OT release in a nucleus-free medium.
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PMID:Estradiol conjugated to BSA releases oxytocin from synaptosome-containing homogenates from the medial preoptic area-hypothalamus. 892 9

The primary objective was to examine the effects of estradiol and the progesterone receptor antagonist onapristone on the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) and ovarian and pituitary oxytocin. A 2 x 2 factorial arrangement of estradiol and onapristone treatments was administered to groups of 5 ewes after destruction of ovarian follicles on Day 8 of the cycle. Estradiol treatments consisted of the administration of a silicone elastomer implant, either containing or not containing estradiol, on Day 8 plus 50 microg of estradiol or corn oil on Days 11 and 12. Onapristone (2 mg/kg) or its vehicle were administered on Day 13, immediately preceding the simultaneous collection of blood samples from the carotid artery, jugular vein, and vena cava at 7.5-min intervals for 7 h. Ewes were immediately killed for measurements of uterine oxytocin receptor concentrations and phosphatidylinositide turnover. More oxytocin pulses were detected in the jugular vein than in the carotid artery (p < 0.01), suggesting that the pituitary is a source of oxytocin. A similar number (p > 0.1) of PGF(2alpha) pulses were correlated with oxytocin pulses as were not. The linked PGF(2alpha) pulses were longer in duration (p = 0.01) with a tendency toward a higher amplitude (p = 0.08). The corresponding vena caval oxytocin pulses had a longer duration (p = 0.02) than those not linked to PGF(2alpha). Estradiol increased oxytocin receptor concentrations and the turnover of phosphatidylinositides (p = 0.02) without affecting PGF(2alpha) pulse characteristics. Onapristone increased (p = 0.03) PGF(2alpha) pulse amplitude. Although a lower than expected temporal correlation between oxytocin and PGF(2alpha) pulses was observed, the distinguishing characteristics of linked pulses may be indicative of their physiological significance.
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PMID:Influence of estradiol and progesterone withdrawal on the secretion of and the temporal correlation between pulses of oxytocin and prostaglandin F2(alpha) in ewes. 916 Jul 23

Bilaterally ovariectomized, nonpregnant female CD rats were studied to investigate the effect of estradiol treatment on in vitro myometrial responsiveness to oxytocin and prostaglandin F2alpha. The first study investigated dose-dependent effects. Seven days after ovariectomy rats were given a single s.c. dose of corn oil (n = 4) or estradiol (5 microg, n = 5; 15 microg, n = 5; 50 microg, n = 4). A second identical injection of corn oil or estradiol was administered 24 h after the initial injection. Rats were killed 48 h after the first injection. A second study investigated time-dependent effects of estradiol treatment. A second group of ovariectomized rats received s.c. estradiol (50 microg) seven days after ovariectomy. These rats were killed either 12 h (n = 5) or 24 h (n = 4) after injection. Full-thickness cross-sections of uteri were suspended in vitro in the longitudinal direction in a superfusion system. Cumulative concentration-response curves were constructed to oxytocin and prostaglandin F2alpha. Both the duration and dose of estradiol treatment significantly (p < 0.05) attenuated baseline contractile activity, and the maximum myometrial response to oxytocin and prostaglandin F2alpha. Estradiol, in a dose-dependent manner, significantly reduced myometrial sensitivity (p < 0.05) for oxytocin and prostaglandin F2alpha.
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PMID:Effect of in vivo estradiol administration to bilaterally ovariectomized rats on in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin. 928 96

Our recent studies have shown that regulation of uterine oxytocin (OT) binding involves at least two different mechanism: Estradiol (E2)-induced upregulation is accompanied by an increase in OT receptor (OTR) mRNA accumulation, implying that the E2 effect is mediated via increased OTR gene transcription and/or OTR mRNA stabilization. In contrast, P (P)-induced OTR down-regulation occurs via a novel non-genomic mechanism, involving a direct interaction of P with the OTR at the level of the cell membrane. We found that P specifically binds to the OTR and inhibits its ligand binding and signalling functions. Physiological levels of P repress in vitro the ligand binding capacity (Bmax) of the OTR by > 50%. When expressed in CHO cells, the OTR provides a high affinity (Kd: 20nM) membrane binding site for P. OT-induced inositol phosphate production and intracellular calcium mobilization is inhibited 85% and 90%, respectively, by P. These effects are specific as signalling and binding functions of the closely related V1a vasopressin receptor remain unaffected by P, and as other, related steroids are devoid of any effect on OTR binding or signalling functions. The present observation of a specific interaction of a steroid with a G-protein-linked receptor defines a new mechanism of non-genomic steroid action and uncovers a novel level of crosstalk between steroid and peptide hormone action.
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PMID:Genomic and non-genomic mechanisms of oxytocin receptor regulation. 1002 16

The aim of this study was to investigate the expression of cytochrome P450 aromatase (aromatase) mRNA, its activity, and estradiol-17beta (estradiol) secretion in bovine corpus luteum (CL) during the estrous cycle. Expression of aromatase mRNA was examined in CL at the early, mid, late, and regressed luteal stages by using a reverse transcription-polymerase chain reaction. Aromatase mRNA was detected in all luteal stages examined, although aromatase expression was significantly lower during the early and regressed luteal phases compared to the mid and late luteal phases. Moreover, cultured midluteal cells clearly converted exogenous [(3)H]androstenedione into estradiol, and an aromatase inhibitor significantly inhibited this conversion. To characterize the local release of estradiol within the CL during the estrous cycle, an in vitro microdialysis system (MDS) of CL was conducted. Estradiol in MDS perfusate was confirmed by a reverse-phase high-performance liquid chromatography in combination with enzyme immunoassays. Basal release of estradiol from microdialyzed CL did not change during the estrous cycle. Additionally, when freshly prepared midluteal cells were exposed to estradiol (10(-14) to 10(-9) M), estradiol stimulated prostaglandin (PG) F(2alpha) secretion (P < 0.05), although it did not affect progesterone and oxytocin secretion. The overall results indicate that estradiol is produced locally in bovine CL throughout the estrous cycle, and they suggest that estradiol plays a role in regulating PGF(2alpha) production in CL as an autocrine/paracrine factor.
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PMID:Estradiol-17beta is produced in bovine corpus luteum. 1171 22

The present study investigated the effects of long-term estradiol withdrawal (ovariectomy) on hypothalamic serotonin-1A (5-HT(1A)) receptor signaling. Changes in neuroendocrine responses to the 5-HT(1A) agonist 8-OH-DPAT and levels of G(z) protein in the hypothalamus were used to examine 5-HT(1A) receptor signaling. Five days following ovariectomy, rats received daily injections of either 2 microg of beta-estradiol 3-benzoate or vehicle (subcutaneously) for 2, 4 or 14 days. Twenty-four hours after the last injection, and 15 min prior to sacrifice, rats were injected with (+/-)8-OH-DPAT (50 micro;g/kg, s.c.) or saline. Estradiol treatment did not alter basal corticotropin (ACTH) or oxytocin levels. Injection of (+/-)8-OH-DPAT produced significant increases in plasma ACTH and oxytocin levels. In the vehicle-treated rats, hormone responses to 8-OH-DPAT were enhanced in rats that received injections for 14 days compared with rats that received injections for either 2 or 4 days. Estradiol treatment for 4 or 14 days blunted this enhanced ACTH response to 8-OH-DPAT, whereas the oxytocin response to 8-OH-DPAT was only blunted after 14 daily injections of beta-estradiol 3-benzoate. The treatment with beta-estradiol 3-benzoate (2 microg/rat) did not reduce membrane-associated G(z) protein levels in the paraventricular nucleus of the hypothalamus. Hence, the inhibitory influence of a low dose of beta-estradiol 3-benzoate on 5-HT(1A) receptor signaling in the hypothalamus is not accompanied by a change in the levels of G(z) protein in the paraventricular hypothalamic nucleus. Results from the present study indicate a supersensitivity of 5-HT(1A) receptors after withdrawal of estradiol and suggest that estradiol suppresses 5-HT(1A) receptor signaling.
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PMID:Ovariectomy-induced increases in hypothalamic serotonin-1A receptor function in rats are prevented by estradiol. 1256 42

Estradiol (E2), progesterone (P4), and oxytocin (OT) are important for the initiation of luteolysis in ruminants but the mechanisms involved are still poorly understood. The objective of this study was to determine if duration of exposure of bovine endometrial epithelial cells to P4 affected the response of the cells to E2. Endometrial epithelial cells, from cows at Days 1-3 of the estrous cycle, were cultured for 10, 17, and 21 days in the presence or absence of P4 (100 ng ml(-1)). After culture, each group of cells was incubated for a further 6, 12, 24 or 48 h with or without E2 (100 pg ml(-1)) and then incubated for 6 h with different doses of OT (2, 20, and 200 ng ml(-1)). E2 enhanced OT-stimulated PGF2 alpha secretion in cells cultured with P4 for 17 or 21 days, with a maximum effect after 24-h exposure, but not in cells cultured with P4 for 10 days. To determine the mechanism of action of E2, COX-1 and COX-2 were measured by Western blotting and OTR number was measured by saturation analysis. OT increased COX-2 (P<0.05), but there was no significant effect of E2 on the expression of either COX-1 or COX-2. E2 did, however, increase (P<0.001) the OTR number in cells cultured with P4 for 21 days, whereas it inhibited OTR in cells cultured for 10 days. These data show that E2 can stimulate PGF2 alpha secretion by increasing OTR expression in bovine endometrial cells in vitro, but only after exposure to P4.
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PMID:Prolonged progesterone treatment of endometrial epithelial cells modifies the effect of estradiol on their sensitivity to oxytocin. 1295 70

The present study examined the effect of estradiol on hypothalamic serotonin-1A (5-HT(1A)) receptor signaling in female rats. We first examined the time-course effects of a single injection of the 5-HT(1A) receptor agonist (+/-)8-OH-DPAT (5, 15 or 30 min prior to decapitation), and dose response of (+)8-OH-DPAT (50, 100, 200 or 500 microg/kg, s.c.) on plasma hormones in ovariectomized rats that received a daily injection of beta-estradiol 3-benzoate (10 microg/day, s.c.) or vehicle (sesame oil) for 2 days. In vehicle- and estrogen-treated rats, the peak response of hormones occurred at 15 min after injection and the time-course of oxytocin and adrenocorticotropic hormone (ACTH) responses to an injection of 8-OH-DPAT were comparable. However, only the oxytocin response was reduced by estrogen treatment. A second experiment compared the ACTH and oxytocin responses with doses of 50 or 200 microg/kg, s.c. of (+)8-OH-DPAT vs. (+/-)8-OH-DPAT in ovariectomized rats that were treated with oil or beta-estradiol 3-benzoate (10 microg/day, s.c.) for 2 days. (+)8-OH-DPAT and (+/-)8-OH-DPAT produced a similar magnitude of increase in plasma levels of ACTH and oxytocin. Treatment with beta-estradiol 3-benzoate produced a significant and comparable reduction in the oxytocin response to the highest dose (200 microg/kg, s.c.) of both (+)8-OH-DPAT and (+/-)8-OH-DPAT but did not alter the ACTH response to either (+)8-OH-DPAT or (+/-)8-OH-DPAT. In the dose-response experiment, a dose of 50 microg/kg of (+)8-OH-DPAT produced a maximal increase in plasma levels of ACTH, while the maximal oxytocin response was achieved with a dose of 200 microg/kg, s.c. Treatment with beta-estradiol 3-benzoate reduced the maximal oxytocin response to (+)8-OH-DPAT (by 29%) but did not alter the ACTH response to any doses of (+)8-OH-DPAT. To examine potential mechanisms mediating the effects of estrogen on 5-HT(1A) receptor signaling, we measured the levels of Galpha(i), Galpha(o) and Galpha(z) proteins, which couple 5-HT(1A) receptors to their effector enzymes, in two subregions of the hypothalamus. The levels of Galpha(z) protein were reduced in the mediobasal hypothalamus (containing the ventromedial and arcuate nuclei), which mainly expresses estrogen receptor-alpha, but not in the paraventricular hypothalamus, which mainly expresses estrogen receptor-beta. Estradiol reduced the levels of Galpha(i2) and Galpha(i3 )proteins in both hypothalamic regions but did not affect Galpha(i1) levels in either area. Combined, the data suggest that racemic and stereoselective 8-OH-DPAT have similar neuroendocrine effects and that both estrogen receptor-alpha and estrogen receptor-beta mediate the reduction in levels of Galpha(i2,3) proteins.
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PMID:Estrogen reduces serotonin-1A receptor-mediated oxytocin release and Galpha(i/o/z) proteins in the hypothalamus of ovariectomized rats. 1538 10


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