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

Endocrine factors involved in the transcriptional regulation of the oxytocin (OT) gene were investigated in heterologous expression systems. Plasmids having a 5'-flanking region of the rat OT gene (-363/+16) or the human OT gene (-382/+41) cloned in front of the firefly luciferase gene were co-transfected with an expression vector for the rat thyroid hormone receptor alpha in P19 embryonal carcinoma (EC) cells. Thyroid hormone (T3) stimulated the activity of the rat and human OT promoters about 10-fold. In MCF-7 breast tumor cells transfected with the human OT promoter-luciferase fusion gene, T3 stimulation through endogenous thyroid hormone receptors was about 5-fold. Co-transfection experiments in P19EC cells using 5' deletion mutants of the rat OT gene showed that thyroid hormone responsiveness was located in two regions, one located between nucleotides -195 and -172, the other between nucleotides -172 and -148. Each region accounted for about 3-fold T3 stimulation. Gel retardation analysis using extracts from HeLa cells over-producing the c-erbA/TR alpha protein showed specific binding to the -172/-148 element, while no binding occurred on the -195/-172 element. The -172/-148 element which contains the imperfect estrogen response element, GGTGACCTTGACC, has inverted as well as direct repeats of the TGACC motif. Mutagenesis of TGACC motifs separately reduced thyroid hormone responsiveness by about 50%. However, simultaneous mutation of two TGACC motifs abolished the responsiveness to T3 completely. There was no cooperativity between the activated thyroid hormone and estrogen receptors in transfected MCF-7 cells nor in thyroid hormone receptor and estrogen receptor co-transfected P19EC cells. Negative interactions between these two receptors were observed and gel retardation assays showed interaction between the two receptors proteins. It was shown in an in vivo experiment that treatment of rats with thyroid hormone increased hypothalamic OT mRNA levels, the pituitary OT content, as well as OT levels in blood. The results reveal thyroid hormone as a physiological regulator of OT gene expression, which stimulates OT promoter activity directly through interaction with a thyroid hormone-response element in the OT gene.
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PMID:Thyroid hormone regulates the oxytocin gene. 137 Dec 78

The immunoperoxidase technique was used on adjacent sections of guinea-pig brain to compare precisely the distribution of estrogen receptor-immunoreactive cells and progesterone receptor-immunoreactive cells in the supraoptic nucleus and the paraventricular nucleus. Only estrogen receptor-immunoreactive neurons were found in the supraoptic nucleus. A large number of estrogen receptor-positive cells were observed in the periventricular magnocellular groups throughout the rostrocaudal extent of the paraventricular nucleus, whereas only a few progesterone receptor-immunoreactive cells were scattered in the anterior portion of this region. We used a combination of axonal tracing with double immunocytochemical detection to determine whether estradiol acts directly on the oxytocin-immunoreactive neurons which project to the neurohypophysis. Oxytocin-immunoreactive cells were found in the supraoptic nucleus, ventrally to the optic pathways, in subchiasmatic and retrochiasmatic areas, and in the anterior hypothalamic area. These cells were also retrogradely labeled by Granular Blue when this tracer was injected intravenously. In the paraventricular nucleus, the Granular Blue/oxytocin-positive cells were observed in the periventricular magnocellular groups whereas Granular Blue labeled neurons were found in both parvocellular and magnocellular components. We found that almost all the oxytocin-immunoreactive cells revealed estrogen receptor immunoreactivity. In conclusion, the comparative study of distribution of estrogen receptors and progesterone receptors in the guinea-pig supraoptic and paraventricular nuclei indicates that, in the supraoptic nucleus, only estrogen receptors are present and that, in the paraventricular nucleus, they are far more numerous than progesterone receptors. The present findings demonstrate that the magnocellular cells which contain estrogen receptors are oxytocinergic. In addition, these cells are retrogradely labeled pointing to a neurohypophysial projection. It is likely that estradiol controls the hypothalamo-neurohypophysial oxytocin system by direct action on the magnocellular neurons.
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PMID:Presence of estrogen receptor immunoreactivity in the oxytocin-containing magnocellular neurons projecting to the neurohypophysis in the guinea-pig. 164 76

DNA sequences in the 5'-flanking region of rat and bovine oxytocin genes were examined for their capacity to confer estrogen responsiveness to their homologous promoters. In contrast to the 5'-flanking region of the rat oxytocin gene, upstream promoter sequences up to 3200 bp of the bovine gene linked to the chloramphenicol acetyltransferase (CAT) reporter gene which were transfected in estrogen receptor expressing MCF-7 cells did not respond to estrogen. Testing 5'-deletion mutants of the rat upstream region linked to the luciferase gene in P19 embryocarcinoma cells co-transfected with an estrogen receptor expression plasmid showed that two regions each associated with approximately 15-fold stimulation of promoter activity were located between nucleotides -172 and -149 and between -148 and +16 in the rat gene. The former region contains the imperfect palindrome GGTGACCTTGACC which differs in one nucleotide from the estrogen response element (ERE) consensus. It is concluded that the corresponding motive CATAACCTTGACC of the bovine gene is not a functional ERE. Thus, the estrogen responsiveness of oxytocin genes is species-dependent.
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PMID:Comparison of the estrogen responsiveness of the rat and bovine oxytocin gene promoters. 199 97

Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be restricted to a subpopulation of OT neurons.
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PMID:The human oxytocin gene promoter is regulated by estrogens. 210 52

The levels of oxytocin receptor (OTR), cytosolic progestin receptor (cPR), cytosolic and nuclear estrogen receptor (cER, nER) were measured in the endometrium of 28 heifers that had been slaughtered on a defined day of the estrous cycle. In an additional, trial endometrial tissue obtained from 78 heifers or cows at the abattoir was analysed for OTR. OTR was absent during the luteal phase (after day 6), but a minor elevation was observed after day 15. OTR increased rapidly after luteolysis on days 17-18 reaching a maximum during estrous on day 21, and decreased again during days 1-6. cER and cPR were different to OTR but followed a similar pattern with maximal levels during days 1-8 of the estrous cycle. At day 12 both receptors were minimal and increased again towards day 21. nER was maximal at day 19-21 coinciding with maximal estradiol levels and estrous. Our data indicate that owing to an increasing sensitivity of the endometrium to progesterone and estradiol after day 12, these steroids may be mainly responsible for the initiation of first PGF2 alpha surges and luteolysis. Oxytocin seems to be of minor importance at this stage owing to low sensitivity of the endometrium for oxytocin.
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PMID:Dynamics of oxytocin, estrogen and progestin receptors in the bovine endometrium during the estrous cycle. 283 97

Rat myometrium exhibited a marked rise in the concentration of oxytocin (OT) receptors during parturition. The elevation began several hours before labor, was maximal during labor, and declined several hours later. In the perinatal period, the change in OT receptor concentration was proportional to the ratio of plasma estradiol to progesterone levels. Several hours before the increase in OT receptor concentration, there was a proportional increase in estrogen receptor concentration in both the cytosol and nuclear fractions of the myometrium. In view of the known action of estrogens in increasing the concentration of OT receptors in rat uterus, we propose that the following sequence of events occurs in the initiation of labor in the rat. The decline in serum progesterone permits estradiol to stimulate the synthesis of estrogen receptors in the myometrium. This increased concentration of estrogen receptors and their occupancy by estradiol stimulates the appearance of more OT receptors, which then trigger labor by interacting with circulating OT.
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PMID:Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term. 624 47

Rats were made unilaterally pregnant by tying the right oviduct on the day after mating, to compare the oxytocin receptor concentrations in a nondistended, nonpregnant uterine horn with those in a distended, pregnant horn. On day 20, they were subjected to bilateral ovariectomy and indwelling balloons were inserted into both uterine horns. Following ovariectomy, the rats were injected im with either oil, estradiol benzoate (5 micrograms/rat per 24 h), or estradiol and progesterone together. For comparison, intact rats were studied on days 21 and 22, 24 and 48 h after insertion of the indwelling balloons. Spontaneous uterine activity and the response to increasing amounts of oxytocin were recorded 20-24 h and 44-48 h after surgery, following which the uteri were excised and assayed for oxytocin and estrogen receptors. The oxytocin receptor concentrations in the two horns were different on day 20 before the treatments were begun, the distended pregnant horn having a higher concentration per milligram DNA than the nonpregnant horn. The various treatments always changed the oxytocin receptor concentrations in the same direction; estrogen increased and progesterone inhibited the estrogen-induced rise in oxytocin receptor concentrations. In intact rats, the distention-induced increase in oxytocin receptor concentrations present on day 20 disappeared near term, but in the absence of the ovaries distention of the uterus had a significant influence on the myometrial oxytocin receptor concentrations, potentiating the effect of estrogen. Progesterone selectively inhibited the distention-induced increase in oxytocin receptor concentrations without inhibiting the hypertrophic effect of distention in general. A good correlation between oxytocin receptor numbers and tissue responsiveness was observed in all instances. The changes in spontaneous activity induced by the various treatments were distinct from the changes in oxytocin responsiveness. Estrogen exerted a strong inhibitory action on the activity stimulated by hormone withdrawal, while progesterone had no inhibitory effect. The pregnant distended horn always showed more spontaneous activity than the nonpregnant horn. There was an overall significant correlation between nuclear estrogen receptor and oxytocin receptor concentrations per milligram DNA, although the partial correlations were not significant in all groups (oil and progesterone).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic and local regulation of oxytocin receptors in the rat uterus, and their functional significance. 631 57

Marked changes in the uterine binding of oxytocin (OT) occur in rats at the time of parturition or after treatment of ovariectomized rats with estrogen or progesterone. To ascertain that these binding sites represent the biological receptors for OT, we measured the uterine response to OT in various groups of rats in which specific OT binding was also determined. Intact pregnant rats and rats ovariectomized on day 20 of gestation and treated thereafter with oil, estradiol benzoate (5 micrograms/24 h), progesterone (5 mg/24 h), or estradiol and progesterone together had indwelling balloons inserted on day 20 for the recording of uterine response to either iv bolus injections or iv infusions of OT. The uterus was removed 24-48 h after balloon insertion, and OT binding to the particulate fraction as well as nuclear estrogen and cytosolic estrogen receptor concentrations were determined. An inverse correlation (r2 = 0.758) was found between the concentration of OT-binding sites and the threshold dose of OT, and a linear correlation was found between the concentration of binding sites and the uterine activity induced by OT infusion (r2 = 0.852). We conclude, therefore, that the high affinity (Kd, 1-2 nM) binding sites for OT represent the physiological receptors. The concentration of these sites increased progressively during estrogen treatment. Progesterone completely inhibited this estrogen-induced rise. After ovariectomy, there was a modest, but significant, increase in OT receptor concentration which also was prevented by progesterone. The increase in OT receptor concentration was correlated with the estrogen receptor concentration in intact pregnant and estrogen-treated ovariectomized animals, but not in the other groups of animals. The apparent affinity of the receptors for OT was not significantly affected by hormone treatment. We conclude that the concentration of receptors is a major factor controlling the uterine responsiveness to OT, and that the receptor concentrations are regulated by ovarian hormones in a manner related to estrogen receptor activation. In addition, estrogen appeared to enhance the coupling of OT receptor occupancy to the tissue response to OT.
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PMID:Correlation between oxytocin receptor concentration and responsiveness to oxytocin in pregnant rat myometrium: effects of ovarian steroids. 687 47

Recently in the pig hypothalamus a vasopressin- and oxytocin-containing nucleus was identified which, like the supraoptic nucleus, becomes sexually dimorphic after puberty. Following the increase in circulating steroids at puberty, the vasopressin- and oxytocin-containing nucleus becomes twice as large in both males and females. In adulthood, the vasopressin- and oxytocin-containing nucleus of females is approximately twice as large as that in males. Because these alterations are possibly due to an influence of gonadal steroids, i.e. estrogens, the vasopressin- and oxytocin-containing nucleus cells were tested for the presence of estrogen receptors. In addition to the area of the vasopressin- and oxytocin-containing nucleus, the present study documented the distribution of estrogen receptors in the septal area and other parts of the hypothalamus of intact post-pubertal male and female pigs, by utilizing immunocytochemical methodology. Intense nuclear estrogen receptor staining was found in a number of areas, i.e. the medial preoptic area, the oxytocin-containing dorsomedial extension of the supraoptic nucleus, a possible homologue of the sexually dimorphic nucleus of the preoptic area, the median preoptic nucleus, the medial and lateral part of the bed nucleus of the stria terminalis, the ventromedial hypothalamus and the arcuate nucleus. In the ventral part of the lateral septum, the septohypothalamic nucleus, the nucleus subfornicalis and the stigmoid nucleus estrogen receptor immunoreactivity was less intense. Dorsolaterally of the vasopressin- and oxytocin-containing nucleus, estrogen receptor positive cells were observed, but the vasopressin- and oxytocin-containing nucleus itself lacked such receptors. In the magnocellular supraoptic nucleus and paraventricular nucleus no nuclear estrogen receptor staining was found. However, a weak cytoplasmic staining was present in all cells. There was a clear sex difference in the estrogen receptor-immunoreactive cell number in a possible homologue of the sexually dimorphic nucleus of the preoptic area. Compared to male pigs, in female pigs the number of cells showing estrogen receptor immunoreactivity in this area, which is known to be sexually dimorphic in various species, was twice as high. In other areas, such as the medial part of the bed nucleus of the stria terminalis, the medial preoptic area, the arcuate and ventromedial hypothalamic nucleus, a similar sex difference was found. In addition estrogen receptor immunoreactivity was generally more intense in females. No sex differences were noted in the overall distribution of estrogen receptor cells in the areas studied.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sex differences in the distribution of estrogen receptors in the septal area and hypothalamus of the domestic pig (Sus scrofa). 770 11

We have recently shown that oxytocin (OT) is synthesized within human amnion, chorion, and decidua during late gestation. The levels of OT messenger ribonucleic acid (mRNA) increased around the time of parturition, suggesting that locally produced OT may play a role in this poorly understood process. In this report, we present results from investigations into the effects of estrogen and progesterone on the synthesis of OT by human chorio-decidua. Using an in vitro incubation system, estradiol at physiological concentrations more than doubled the concentration of OT mRNA. This was reflected by an increase in the amount of OT peptide secreted into the medium. The increase in OT mRNA was antagonized by tamoxifen, suggesting that the effects were estrogen receptor mediated. Progesterone had no effect on OT mRNA synthesis. Using ribonuclease protection assays, mRNAs for estrogen receptor (ER) and progesterone receptor (PR) were detected in all tissues examined. The highest levels were found in decidua, with lower amounts in chorion and very small amounts in amnion and placenta. This is the same relative tissue distribution that we previously demonstrated for OT mRNA. A single transcript was present for ER, and two transcripts were protected for PR. The concentrations of ER mRNA in chorio-decidua were 3-fold higher in tissues obtained after spontaneous labor onset than in tissues obtained from cesarean section at a similar gestational age but before labor onset. Levels of PR did not change significantly. We conclude that synthesis of OT in human chorio-decidua may be regulated in part by estrogen, and that regulation of ER levels may be an important factor modulating this effect. These data support the hypothesis of a paracrine network within human fetal membranes and decidua that may participate in regulating the timing of human birth.
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PMID:Estrogen stimulates oxytocin gene expression in human chorio-decidua. 785 22


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