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)

A synthetic 45-mer oligonucleotide corresponding to part of the ovine endometrial oxytocin receptor cDNA was hybridized to sections of ovine uterus collected from 40 ewes at different stages during the oestrous cycle, the first 3 weeks of pregnancy and seasonal anoestrus. The quantity of oxytocin receptor mRNA was measured as the optical density (OD) value on autoradiographs using image analysis. Message first appeared in the luminal epithelium on days 14-15 of the cycle, increasing to a peak OD of 0.48 at oestrus and decreasing again between days 2 and 5. Oxytocin receptor mRNA in the superficial glands, deep glands and caruncular stroma increased between day 15 and oestrous to peak OD values of 0.17, 0.11 and 0.11 respectively, declining again by day 2 and reaching basal values (OD < 0.015) by day 5. Hybridization to the myometrium tended to rise from a mean OD value of 0.01 on days 2-15 to a peak of 0.03 +/- 0.01 (mean +/- S.E.M.) on days 0-1, but the change was not significant. In pregnant ewes there was no detectable oxytocin receptor mRNA on days 14-15 in any region, but hybridization to the luminal epithelium was present in two of three ewes on day 21. In anoestrous ewes oxytocin receptor mRNA concentrations in all areas of the endometrium were approximately half those measured at oestrus. Optical density readings for oxytocin receptor mRNA in the various uterine compartments were compared with measurements of oxytocin receptors in the same regions as assessed by binding studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin (125I-labelled OTA). In the endometrium, receptor mRNA and 125I-labelled OTA binding patterns changed in parallel, and both sets of measurements were significantly correlated (P < 0.01). In the myometrium, a significant increase in 125I-labelled OTA binding occurred at oestrus; this was not accompanied by a similar increase in oxytocin receptor mRNA hybridization. This study helps to confirm that the previously identified cDNA clone is derived from the ovine oxytocin receptor, as patterns of oxytocin receptor mRNA expression in the endometrium closely resembled those of oxytocin binding. Maximum expression and binding both occurred at oestrus, suggesting that regulation of the oxytocin receptor gene in the uterus occurs principally at the transcriptional, rather than at the translational, level. Failure to detect a significant increase in myometrial mRNA expression at oestrus may indicate that the endometrial and myometrial oxytocin receptors are of different isoforms.
J Mol Endocrinol 1994 Feb
PMID:Localization of oxytocin receptor mRNA in the ovine uterus during the oestrous cycle and early pregnancy. 818 18

The initiation of human parturition remains an enigma but is thought to involve a number of hormonal signals such as oxytocin and prostaglandins. One other possible signal is placentally derived corticotropin-releasing hormone (CRH). We have recently reported that the human myometrium expresses a specific receptor for CRH which changes to a high affinity state prior to term. In view of this we sought to determine whether this receptor is functionally linked to some of the known modulators of myometrial function. Myometrial membranes were prepared by differential centrifugation from either pregnant (caesarian section) or non-pregnant (hysterectomy) myometrium. For binding studies the membranes were incubated with radiolabelled oCRH at 22 degrees C for 2 h. For second messenger studies they were incubated at 37 degrees C for 10 or 30 min with either 0.5 mM ATP and 10 mM theophylline (cAMP) or 0.05 mM arachidonic acid or 0.5 mM linoleic acid (PGE2). When increasing concentrations of membranes were incubated with radiolabelled oCRH an interesting phenomenon was observed. In non-pregnant membranes the binding reached a plateau, whereas in membranes prepared from pregnant myometrium, the binding decreased at concentrations above 130 micrograms/ml. Possible explanations for this phenomenon include an inhibitor which prevents ligand-receptor binding or an enzyme which destroys the receptor binding region of the ligand. Incubation of both types of membranes with GTP or its analogue, GppNHp, resulted in a dose-dependent inhibition of specific binding suggesting that the myometrial CRH receptor is linked to a G regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Mar
PMID:The human myometrial CRH receptor: G proteins and second messengers. 820 32

In addition to their classical hormonal role, the neurohypophyseal peptides vasopressin (AVP) and oxytocin (OT) are also implicated as regulators of growth and development. Mitogenic actions of AVP are particularly well characterized and may underly the potential role of AVP as an autocrine regulator of tumor growth. Effects of AVP and OT on neural development are suggested by numerous studies, but definitive physiological evidence is lacking. Current studies on the molecular characterization of AVP and OT receptors, and on transgenic animals will provide insights into the developmental actions of neurohypophyseal peptides.
J Mol Neurosci 1993
PMID:Neurohypophyseal peptides as regulators of growth and development. A review. 831 55

Transcription factors of the steroid/thyroid hormone receptor superfamily are mediators of development and regulation of the brain. Previous studies have shown that the hypothalamic oxytocin (OT) gene is a potential target of these receptors, since its promoter is stimulated by estrogens and thyroid hormone. Here it is shown that the rat OT promoter is stimulated (at least 20-fold) by retinoic acid through two distinct regions in the 5'-flanking region. The major retinoic acid response element was located between nucleotides -172 and -148 and a minor one between nucleotides -112 and -77, as concluded from the transactivation of 5'-deletion mutants and binding to promoter elements by the retinoic acid receptor. Since the -172/-148 element also conferred estrogen and thyroid hormone responsiveness, it can be considered a composite hormone response element. This element contains a natural variant of the direct repeat of the half-site AGGTCA with spacing zero (DR-0) as well as a palindrome. Analysis of the core sequences of this element by site-directed mutagenesis showed that each of the three TGACC motifs integral to this element contributes to the multihormone sensitivity, but the contribution of each motif is different for the individual receptors. In neonatal rats, vitamin A deficiency and retinoic acid supplementation did not cause changes in hypothalamic OT mRNA levels and OT peptide levels in the pituitary gland and plasma. Gel-retarded protein-DNA complexes were formed between the composite hormone response element and extracts of the hypothalamic supraoptic and paraventricular nuclei. The composite hormone response element has a unique configuration and integrates responses of multiple members of the steroid/thyroid hormone receptor superfamily.
Mol Endocrinol 1993 Jan
PMID:A composite hormone response element mediates the transactivation of the rat oxytocin gene by different classes of nuclear hormone receptors. 838 87

We have previously characterized specific oxytocin receptors in the rat anterior pituitary gland, using a highly selective oxytocin receptor antagonist as radioligand. The aim of the present study was to examine whether occupation of these receptors by oxytocin produces a stimulation of prolactin release and a rise in the accumulation of total inositol phosphates in the rat adenohypophysis. Anterior pituitary cells harvested from randomly cycling and diethylstilboestrol (100 micrograms s.c.)-treated rats were perifused with Dulbecco's minimal essential medium at a rate of 0.3 ml/min. Oxytocin and the specific oxytocin agonist [Thr4-Gly7]-oxytocin (TG-OT) both stimulated a significant prolactin release at concentrations of 10(-6) and 10(-7) M. Oestrogen treatment did not affect the response to oxytocin, indicating that there is no straightforward correlation between receptor number and prolactin secretory response in the rat pituitary gland. The involvement of phosphoinositide hydrolysis was investigated in dispersed anterior pituitary cells and uterine tissue from randomly cycling rats. Oxytocin and arginine-vasopressin stimulated a significant (P < 0.05) and dose-related increase in total inositol phosphates, vasopressin being more potent. The specific oxytocin agonist TG-OT had no effect on total inositol phosphate production in pituitary cells, but when tested in uterine tissue it significantly (P < 0.05) stimulated the accumulation of total inositol phosphate at all concentrations tested (10(-5) to 10(-9) M). In conclusion, the data show that oxytocin has prolactin-releasing activity, acting on specific receptors in the anterior pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1993 Apr
PMID:Specific oxytocin agonist stimulates prolactin release but has no effect on inositol phosphate accumulation in isolated rat anterior pituitary cells. 838 9

This study determined whether twice-daily intrauterine injections of ovine conceptus secretory proteins (oCSP) containing type-I trophoblast interferon (25 micrograms/uterine horn) from day 11 to day 15 post-oestrus (oestrus = day 0) could alter the binding capacities of endometrial receptors for oxytocin, progesterone and oestrogen in cyclic ewes when compared with control ewes receiving serum protein (SP) injections. Injections of oCSP on days 11-15 post-oestrus decreased concentrations of oestrogen receptors (P < 0.06), oestrogen receptor mRNA (P < 0.05) and progesterone receptors (P < 0.08) in endometrium on day 16 when compared with SP-infused control ewes, which were undergoing corpus luteum regression on days 14-16. Injection of oCSP also decreased the number (P < 0.10) and affinity (P < 0.06) of oxytocin receptors. Inositol phosphate formation induced in the endometrium on day 16 by 100 nM oxytocin in vitro was highly correlated with the concentration (r > or = 0.93, P < 0.001) and Kd (r = -0.91, P < 0.01) of oxytocin receptors in SP-infused ewes, but was not as highly correlated with concentration (r < or = 0.83, P < 0.06) and Kd (r < or = 0.40, P > 0.40) of oxytocin receptors in oCSP-infused ewes. This indicates that oCSP disrupted the relationship between oxytocin receptor binding and oxytocin-induced activation of its second messenger system. These results indicate that antiluteolytic type-I trophoblast interferon may prevent oxytocin-induced luteolytic pulsatile secretion of prostaglandin F2 alpha during maternal recognition of pregnancy in sheep, by reducing the synthesis and affinity of endometrial oxytocin receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1993 Apr
PMID:Changes in progesterone and oestrogen receptor mRNA and protein and oxytocin receptors in endometrium of ewes after intrauterine injection of ovine trophoblast interferon. 838 10

This study characterized changes in levels of mRNA and protein for endometrial oestrogen receptors (ERs) and progesterone receptors (PRs) during luteolysis and maternal recognition of pregnancy. For cyclic and pregnant ewes, endometrium was collected on days 10, 12, 14, or 16 post-oestrus (4 ewes/day for each status) for the measurement of ER and PR mRNA and protein. The amount of receptor mRNA is expressed in relative units above background, measured from radiographs of dot-blot hybridization of total endometrial RNA with ER and PR cDNAs. At hysterectomy, jugular vein blood samples were collected and assayed for progesterone, total corpus luteum weight was recorded and, in vitro, endometrial oxytocin-stimulated inositol phosphate formation was estimated. In pregnant ewes, plasma progesterone increased gradually between days 10 and 16 (P < 0.01), corpus luteum weight was stable at approximately 0.8 g and oxytocin did not stimulate endometrial formation of inositol phosphates in vitro. In contrast, in cyclic ewes, plasma progesterone decreased from day 10 to day 16 (P < 0.01), corpus luteum weight decreased after day 14 to approximately 0.48 g (P = 0.05) and oxytocin stimulated an increase of approximately 1300% in the endometrial formation of inositol phosphates on day 16. cDNAs specifically hybridized with 1.6 and 3.1 kb transcripts for PR mRNA and a 6.5 kb transcript for ER mRNA. In cyclic ewes, the amount of PR mRNA increased from day 10 to maximum levels on days 14-16. The number of PRs decreased from day 10 (2.25 pmol/mg DNA) to day 12 (0.98 pmol/mg DNA) and then increased from day 14 to day 16 (2.8 pmol/mg DNA). In pregnant ewes, PR mRNA levels were greatest on days 10-12 and decreased by approximately 50% by day 16. In contrast, the number of PRs was relatively unchanged from day 10 to day 16 (1.53 to 1.03 pmol/mg DNA). In cyclic ewes, the amount of ER mRNA was lowest at day 10 and increased fivefold by day 16. The number of ERs remained relatively unchanged from day 10 to day 14 (6.07 pmol/mg DNA) and increased by day 16 (16.12 pmol/mg DNA). In pregnant ewes, ER mRNA decreased by approximately 80% from day 12 to day 16. Similarly, the number of ERs decreased from day 10 to day 16 (5.41 to 2.05 pmol/mg DNA). Correlations between ER mRNA and PR mRNA (r = 0.68), ERs and PRs (r = 0.50) and ER mRNA and ERs (r = 0.50) were high (P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1993 Apr
PMID:Changes in progesterone and oestrogen receptor mRNA and protein during maternal recognition of pregnancy and luteolysis in ewes. 848 65

Large conductance, Ca(2+)-activated K+ channels are believed to underlie interburst intervals and, thus, contribute to the control of hormone release from neurohypophysial terminals. Because ethanol inhibits the release of vasopressin and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+ channels from these terminals using patch-clamp techniques. Ethanol (10-100 mM) applied to the cytosolic surface of excised, inside-out patches reversibly increases channel activity in a concentration-dependent manner, reaching a plateau at 50-100 mM. This activation is not mediated by freely diffusible cytosolic second messengers or the release of Ca2+ from intracellular stores. Rather, it likely reflects a direct interaction of ethanol with the channel protein or a closely associated component. Neither the unitary conductance nor the characteristics of the voltage-current relationship are modified by the drug. The increase of channel activity by ethanol results from a modification of channel gating properties: the contribution of long openings to the total time spent in the open state is increased, the average duration of the fast openings is slightly increased, and long closures disappear in the presence of the drug. The activation of large conductance, Ca(2+)-activated K+ channels by ethanol, in conjunction with the previously reported inhibition of voltage-dependent Ca2+ channels, can explain the reduced release of vasopressin and oxytocin after ethanol ingestion.
Mol Pharmacol 1996 Jan
PMID:Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels in isolated neurohypophysial terminals. 856 10

Receptors of oxytocin were found to occur in the membrane fraction obtained from longitudinal muscle of pregnant rat uterus. The affinity of the membrane receptor for oxytocin increased through an increase in the association rate and a decrease in the dissociation rate during gestation. The membrane oxytocin receptor concentrations rose almost three-fold from Day 15 to Day 21. A transition of oxytocin receptors from a single class of independent sites to site-site interacted multiple binding sites, which most likely exhibit positive cooperativity during the last seven days of gestation, was observed. These results suggest that changes in the dynamics of uterine oxytocin receptors also play an important role in the onset of labor.
J Mol Recognit
PMID:Changes in kinetic properties of oxytocin receptors in longitudinal muscle membranes of rat uterus during gestation. 857 53

Oxytocin (OT) and its mRNA are expressed at very low levels in granulosa cells from bovine preovulatory follicles isolated before the LH/FSH surge and increase dramatically between the surge and ovulation. We have shown previously that OT stimulates progesterone secretion by granulosa cells obtained before, but not after the gonadotropin surge, suggesting that OT may be involved in the follicular/luteal phase shift in steroidogenesis from estradiol/androgen to progesterone. One objective of this study was to determine if OT affects estradiol as well as progesterone production by utilizing culture conditions that maintain estradiol secretion in vitro. A second objective was to determine if OT regulates steroidogenesis by effects on the levels of mRNA for the steroidogenic enzymes involved in progesterone synthesis, cytochrome P450 side-chain cleavage (P450scc) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), or in estradiol production, cytochrome P450 aromatase (P450arom). Granulosa cells were isolated from bovine preovulatory follicles and cultured for 3 days with or without OT in medium supplemented with either insulin (1 microgram/ml) + 1% fetal calf serum (FCS), which maintains basal estradiol secretion, or low doses of FSH (1 and 2 ng/ml) + 1% FCS, a culture condition that maximizes effects of FSH on estradiol secretion. After the first day of culture, OT stimulated progesterone (P < 0.01) and inhibited estradiol production (P < 0.01) in both control and FSH-treated cultures. In contrast, OT had only a small stimulatory effect on the levels of mRNA for P450scc and 3 beta-HSD and no effect on mRNA for P450arom. These findings suggest that: (1) OT plays an autocrine role in regulating the follicular luteal phase shift in steroidogenesis by both increasing progesterone and inhibiting estradiol production and (2) the differential effects of OT on steroid production are not mediated primarily by effects on levels of mRNA for steroidogenic enzymes.
Mol Cell Endocrinol 1996 Feb 05
PMID:Differential effects of oxytocin on steroid production by bovine granulosa cells. 864 19


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