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

The effects of the uterine relaxants relaxin and isoproterenol on intracellular free calcium and inositol phosphate formation were investigated in rat myometrium. Preincubation of fura-2-loaded myometrial cell suspensions with relaxin and isoproterenol inhibited the oxytocin-induced stimulation of intracellular free calcium, with EC50 values of 0.02 and 1.0 microM, respectively. Pretreatment of cells with pertussis toxin or replacement of extracellular calcium with 2 mM EGTA inhibited the oxytocin-induced increase in intracellular calcium by 47% and 50%, respectively, but did not inhibit the action of relaxin. (Bu)2cAMP and forskolin also inhibited the effect of oxytocin on intracellular calcium. In uterine strips prelabeled with [3H]inositol, oxytocin stimulated a dose-dependent accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate, with and EC50 of 0.38 microM, and pertussis toxin inhibited this effect. Relaxin, isoproterenol, chlorophenylthio-cAMP, and forskolin inhibited the oxytocin-stimulated formation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. The effect of relaxin on inositol trisphosphate formation was dose dependent, with an EC50 of 0.1 microM. Relaxin and isoproterenol also inhibited inositol phosphate formation in myometrial cells. These data demonstrate the attenuation of contractant-induced elevation in myometrial intracellular calcium and phosphoinositide turnover by uterine relaxants and suggest that these actions may be related. In addition, they provide additional evidence that cAMP-mediated mechanisms may be involved in mediating uterine relaxation.
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PMID:Antagonism of contractants and relaxants at the level of intracellular calcium and phosphoinositide turnover in the rat uterus. 254 7

The utero-ovarian veins and lymph vessels are intimately connected with the ovarian artery in the human female and in domestic animals, with the exception of the horse and the human female. A direct, local exchange of molecules from veins and lymph vessels to arteries (counter current transfer) has been documented for this anatomic structure. Countercurrent transfer of certain inert gases (133xenon, 85krypton), of prostaglandins (PGF2 alpha), of steroid hormones (e.g. progesterone, estradiol, testosterone), and of small peptide hormones (oxytocin, relaxin) has been shown to occur in laboratory and domestic animals as well as in the human female. The transfer of the inert gases takes place within seconds. The transfer of steroid hormones and peptides is detectable within minutes while the transfer of PGF2 alpha is delayed for 20 minutes. Red blood cells or albumin are not transferred. The existence of the local transfer is postulated to be of importance for: 1) the pregnancy/non-pregnancy signal from the uterus and tube to the ovary. The signal may be a combination of a luteotrophic signal from the embryo and lack of a "non-pregnant" luteolytic signal from the endometrium, the latter probably being PGF2 alpha in some species; 2) the unilateral influence of the ovarian hormones on the function of the ovarian, tubal, and possibly uterine tissues. An active corpus luteum may create in a mono-ovulatory animal a higher progesterone level in arterial blood supplying the ipsilateral tube and ovarian interstitial tissue than on equivalent contralateral organs.
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PMID:Counter current transfer in the female adnex. 255 25

1. The actions of angiotensin II, bradykinin, oxytocin, arginine vasopressin, relaxin, serotonin and the prostaglandins E2 and F2 alpha were examined on preparations of costo-uterine muscle from stilboestrol-treated rats. 2. All the agonists, except relaxin, when used in concentrations which contract the rat uterus, also produced contractions of costo-uterine muscles. Concentration-response curves were steep and maximal responses to the agonists were comparable. The negative log molar EC50 values were: serotonin, 6.5; angiotensin II, 8.8; bradykinin, 8.4; PGE2, 8.3; PGF2 alpha, 7.1. The EC50 values (units/L) for oxytocin and vasopressin were 4.4 and 2.7 respectively. 3. Indomethacin (2.8 or 5 mumol/L) did not decrease the contractile effects of the peptides or serotonin. The effects of serotonin were reduced, but not reversed, by methysergide (0.94 mumol/L). 4. Porcine relaxin inhibited field stimulation-induced contractions of costo-uterine muscle and uterine horns from immature rats pretreated with oestradiol cypionate and from stilboestrol-treated mature rats. It was much less potent, and its effects were less clearly concentration-related, on costo-uterine muscle. 5. The inhibitory effects of relaxin on the uterus were unaffected by propranolol (1 mumol/L), confirming that on this tissue relaxin acts independently of the release of catecholamines. Progesterone (30 mumol/L) was also without effect on the action of relaxin on the uterus. 6. These results taken together indicate that the costo-uterine muscle of the rat: (i) contracts in response to serotonin and the peptides angiotensin II, arginine vasopressin, bradykinin and oxytocin independently of the release of the contractile prostaglandins F2 alpha and E2; and (ii) in contrast to the uterus, may lack a significant population of receptors for relaxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of some autacoids and peptides, including relaxin, on costo-uterine muscle from rats. 257 64

To test the interaction of various hormones on the myometrium, the following experiments were done studying in vitro contractile activity of uterine segments from immature rats. The rats were divided into two groups: group 1 animals were treated with estrogen (n = 9) and group 2 animals were treated with both estrogen and progesterone (n = 11). Uteri from animals in each group were removed and segments were maintained in a temperature- and pH-controlled organ bath. After baseline contractions were established, uterine segments were treated with either oxytocin and then relaxin, or relaxin and then oxytocin. The dose of relaxin used, 20 ng/ml, was previously shown to be effective in inhibiting uterine contractions of animals treated with either estrogen or estrogen plus progesterone. The dose of oxytocin, 2.5 mlU/ml, was the maximal effective dose shown not to produce prolonged tetany. Estrogen plus progesterone treatment increased the frequency of contractions and resulted in contractions of greater duration of the maximal contractile force, as compared with treatment with estrogen alone. Oxytocin caused a stimulation of contractions in relaxin-inhibited uterine strips. Relaxin decreased the hypertonic contractions produced by oxytocin treatment, resulting in contractions similar to baseline. These data demonstrate that oxytocin and relaxin are directly antagonistic in their effects on uterine contractility. This suggests that labor may occur as a result of increased sensitivity to oxytocin or a decreased sensitivity to relaxin.
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PMID:The antagonistic effect of oxytocin and relaxin on rat uterine segment contractility. 260 21

The effects of porcine relaxin (3000 units/mg) on oxytocin (OT) and progesterone secretion were studied in beef heifers on Day 274 (10 days before expected parturition). Heifers (n = 11) were randomly assigned to three treatments: relaxin iv infusions combined with im injection (RLX-INF, 9000 units), relaxin im injection (RLX-im, 6000 units), and phosphate-buffered saline-treated controls (PBS). RLX-INF heifers received infusions of PBS and 1000 units of relaxin for 165 min, followed by 2000 units of relaxin im and finally 2000 units of relaxin infusion followed by 4000 units of relaxin im. Endogenous relaxin (immunoreactive) in the PBS-treated group was 0.2-0.9 ng/ml peripheral plasma. For the RLX-im group, peak relaxin was 81 +/- 12 ng/ml (+/- SE) at 45 min after treatment. There were two peaks of relaxin, 18 +/- 5.3 ng/ml and 74 +/- 7.5 ng/ml, 3.5-4.5 hr apart in the RLX-INF group. Significant peak releases of OT were evident in the relaxin-treated heifers. For the RLX-im group, an OT peak (42 +/- 16 pg/ml) occurred within 30 min after relaxin treatment. For the RLX-INF heifers, 2000 and 4000 units of relaxin were associated with major peaks of 14 +/- 0.5 and 43 +/- 1.7 pg/ml OT, respectively. Basal OT plasma levels in the PBS group were 2.5-3.1 pg/ml. Mean plasma progesterone for all heifers was 6.2 +/- 2.11 ng/ml before treatment. There was a significant decrease in progesterone (-2.5 ng/ml) in the RLX-im group within 60 min after relaxin treatment and 45 min after peak OT secretion. The maximum decrease in progesterone (-3.2 +/- 0.68 ng/ml) occurred 135 min after treatment in the RLX-im group. In the RLX-INF group, 2000 units of relaxin infusion combined with 4000 units of relaxin im significantly decreased progesterone (-3.2 +/- 1.59 ng/ml) in peripheral plasma. These results clearly indicate that relaxin causes an acute peak release of oxytocin within 30 min, followed by a marked decrease in plasma progesterone concentration in late-pregnancy cattle.
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PMID:Relaxin regulates oxytocin secretion in late-pregnant beef heifers. 272 77

The effect of porcine relaxin on myometrial activity was studied in 18 nonpregnant and 54 pregnant pigs. Relaxin inhibited spontaneous contractility in all luteal phase and pregnant pigs. However, similar doses of relaxin had no effect on oxytocin-, prostaglandin E2- or prostaglandin F2 alpha-induced contractions. Only when the doses were increased fivefold to sixfold, to nonphysiologic levels, did relaxin inhibit the action of these oxytocic agents. The effect of relaxin was the same throughout pregnancy. This finding helps explain the two paradoxical roles of relaxin: it inhibits spontaneous myometrial contractility during pregnancy and thus preterm labor but is able to facilitate labor at term through its cervical ripening action without inhibiting the oxytocin- and prostaglandin-driven contractions of parturition.
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PMID:Effect of porcine relaxin on spontaneous, oxytocin-driven and prostaglandin-driven pig myometrial activity in vitro. 279 65

In primates, the endocrine signals which correlate with the end of gestation, i.e. account for fetal maturity, and initiate the parturition, i.e. trigger the myometrium contractility, remain unknown. Direct and indirect evidence supports the view that, as with domestic mammals, progesterone (or the estrogen/-progesterone ratio) plays a prominent role in inhibiting the contractility of the pregnant uterus. In the past few years an increasing number of endocrine factors have been identified in the placenta. They may contribute to the control of local or systemic steroid production but their effects are extraordinarily intermingled and it is impossible today to state whether any of them are relevant to the mechanism of parturition. The trophoblast and the myometrium establish close contact in the primate pregnancy. This is evidenced by histological studies and also by the influence of the proximity of the placenta on tissue steroid concentrations and the mechanisms of hormone coupling in the myometrium. Specific types or subtypes of myometrium hormone receptors are now well identified (e.g. to oxytocin, to catecholamines) and this now permits a better understanding of the role of their endogenous agonists in the course of parturition. However, such data are still lacking for other factors (e.g. prostanoids, VIP, relaxin...) involved to varying degrees in this process.
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PMID:[Hormones and parturition in primates]. 282 68

Two mares received PGF-2 alpha twice daily until abortion and 2 mares received a combined treatment with oestradiol benzoate and oxytocin. The mares were about 150 days pregnant. The PG-treated animals aborted after 37 and 61 h, respectively, and the fetuses were expelled in intact fetal membranes. The other 2 mares aborted 13 and 27 h after the first oxytocin injection, respectively, and showed strong uterine contractions and expelled the fetuses in disrupted fetal membranes. Concentrations of 15-ketodihydro-PGF-2 alpha increased both after PG and oxytocin injections and in association with the abortion, but after the PG-induced abortion there was an immediate return to basal levels and after the oxytocin-induced abortion there was a large increase in the concentrations, indicating damage of the uterus. Progesterone and relaxin concentrations followed the placental function and decreased in association with the abortions. Oestrone sulphate values differed in the two groups; the oxytocin-treated animals showed a rapid decrease while the mares treated with PG showed first a marked increase and then a decrease. Concentrations of PMSG appeared to be unaffected by the abortions.
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PMID:Hormonal changes associated with induced late abortions in the mare. 282 69

To determine whether the human corpus luteum is a source of relaxin and oxytocin, we measured the concentrations of these peptides in plasma obtained from the ovarian veins of ovaries with and without a corpus luteum and compared these to peripheral plasma levels. Peripheral and ovarian venous blood samples were obtained from 34 nonpregnant women, 13 during the luteal phase and 21 during the follicular phase of their cycles, and from a 6-week pregnant woman. Plasma relaxin, oxytocin, and progesterone concentrations were determined by sensitive and specific RIAs. Plasma relaxin levels were not detectable (less than 0.16 microgram/L) in peripheral or ovarian venous plasma not draining a corpus luteum. The mean relaxin concentration in plasma draining an ovary with a corpus luteum was 0.41 +/- 0.09 (+/- SE) microgram/L. Oxytocin levels also were significantly higher in plasma draining an ovary with a corpus luteum (6.70 +/- 1.86 pmol/L) than in that draining the ovary with no corpus luteum (1.58 +/- 0.09 pmol/L; P less than 0.01) or in peripheral plasma (1.58 +/- 0.09 pmol/L; P less than 0.025). The mean progesterone concentration also was highest in plasma draining an ovary with a corpus luteum (210.2 +/- 50.5 nmol/L) compared with those in plasma from the contralateral ovarian vein (40.3 +/- 16.5 nmol/L P less than 0.005) and peripheral plasma (30.2 +/- 5.7 nmol/L; P less than 0.005) during the luteal phase. In a woman who was 6 weeks pregnant, plasma draining the ovary with a corpus luteum had 1.9 micrograms relaxin/L, but only 0.49 pmol/L oxytocin; the latter was similar to concentrations in noncorpus luteum-bearing ovarian venous plasma. These findings indicate that the human corpus luteum secretes relaxin, oxytocin, and progesterone. Both ovarian oxytocin and relaxin may function as paracrine or autocrine modulators of luteal function.
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PMID:Human corpus luteum secretion of relaxin, oxytocin, and progesterone. 291 60

The shape of rat myometrial cells in culture was altered by exposure to hormones. Oxytocin (107 microU/ml) significantly decreased mean cell length and area. Treatment of oxytocin-treated cells with relaxin (1.5 micrograms/ml), isoproterenol (10 microM) or (Bu)2 cAMP (1 mM) for 15 min resulted in a significant increase in cell length and area. The effect of relaxin was time dependent, with a significant increase in cell length by 1 min and in cell area by 3 min. Relaxin elicited a concentration-dependent increase in cell length and area between 0.1 and 2 micrograms/ml. The actions of relaxin correlate in time course and concentration dependence with its effects on cAMP elevation in the presence of 0.4 microM forskolin and on changes in myosin light chain kinase kinetic parameters in these cells. Myometrial cells in culture constitute a useful model system in which to correlate physical and biochemical effects of relaxin and other hormones.
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PMID:Relaxin affects the shape of rat myometrial cells in culture. 300 54


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