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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human granulosa cells synthesize and secrete the oxytocin hormone. We have already shown that oxytocin-Gly, the last post-translational maturation intermediate of pro-hormone, is largely secreted by cultured granulosa cells deprived of ascorbate (Plevrakis et al. (1990) J. Endocrinol. 124, R5-R8). Using a combination of high performance liquid chromatography and radioimmunoassay, the oxytocin-like material present in human granulosa cell extracts, in follicular fluid, in cultured granulosa cell supernatants and in corpora lutea extracts was identified. We have demonstrated the presence of oxytocin-Gly, oxytocin-Gly-Lys and oxytocin-Gly-Lys-Arg, the same post-translational maturation intermediates as those we identified in bovine corpus luteum secretory granules. Thus we conclude that post-translational maturation of pro-oxytocin/neurophysin in human ovary proceeds by the same proteolytic events as those we described in bovine post-pituitary gland and corpus luteum.
Mol Cell Endocrinol 1992 Feb
PMID:COOH-terminally-extended processing forms of oxytocin in human ovary. 154 13

Expression of the gene encoding the oxytocin precursor occurs in the hypothalamus and, to a lesser extent, in a number of peripheral organs, the tissue-specific regulatory mechanisms of which are largely unknown. By DNA sequence analysis several elements upstream of the transcriptional start point of the rat oxytocin gene were identified matching the consensus sequence of enhancers inducible by estrogen or glucocorticoids, respectively. Their general transactivating capacities were investigated using heterologous gene constructs and revealed that the rat oxytocin gene harbours two functional estrogen responsive elements near the transcription initiation site, one of which is conserved in the respective human gene. In addition, one enhancer conferring glucocorticoid responsiveness to a reporter gene is located at nucleotide residues -2449 to -2464. These data might indicate a steroid hormone-mediated influence on oxytocin gene expression in the central nervous system and/or the periphery.
Brain Res Mol Brain Res 1991 Mar
PMID:Functional characterization of estrogen and glucocorticoid responsive elements in the rat oxytocin gene. 164 32

Oxytocin (OT) and V1 vasopressin (VP) receptors are present simultaneously in several tissues, including the uterus. In myometrium these receptors mediate contractility, while in endometrium they mediate the release of other uterotonic substances as endothelin (ET). In rabbit myometrium, estrogens increase, while progesterone blunts neurohypophysial hormone receptors. However, the action of sex steroids on OT and V1 VP receptors differs in terms of the ED50 and maximal effect. Therefore, at parturition, only OT receptors show a dramatic rise, while V1 VP receptors do not change, suggesting a major role for OT in labor. ET is a potent stimulator of uterine activity acting through specific receptors present on myometrial cells. These receptors as well as the endometrial localization of ET are modulated by sex steroids, indicating that ET might represent a paracrine regulator of uterine activity. In humans, OT but not V1 VP receptors increase as pregnancy progresses, confirming the primary relevance of OT in timing delivery.
J Steroid Biochem Mol Biol 1991
PMID:Steroid modulation of oxytocin/vasopressin receptors in the uterus. 165 85

Oxytocin is produced in the granulosa-derived cells of the ruminant corpus luteum where its gene is dramatically up-regulated within days of ovulation. Regulation of these processes is poorly understood but oxytocin release can be increased by insulin, insulin-like growth factor I (IGF-I), and gonadotropins. Here we have assessed interactions between these regulatory systems. Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG) caused dose-dependent release of oxytocin from bovine granulosa cells cultured in medium containing 100 ng/ml insulin. The gonadotropins also increased oxytocin mRNA levels and their effects were mimicked by forskolin. The effects of these stimuli on oxytocin and progesterone release were synergistically increased by insulin or IGF-I. Binding studies revealed separate binding sites with characteristics of insulin and IGF-I receptors. Insulin potentiated the effects of hCG and forskolin on oxytocin mRNA levels and release of oxytocin and progesterone in cells from follicles containing greater than 50 ng/ml estradiol. In cells from follicles containing less than 5 ng/ml estradiol these stimuli had little effect on oxytocin release although progesterone release was synergistically increased by insulin and forskolin. The data suggest that gonadotropins regulate oxytocin synthesis and release and that these effects are amplified by insulin or IGF-I acting via their own receptors. Changes associated with maturation of the target cells in vitro appear prerequisite for oxytocin production in response to increased cAMP levels in the presence of insulin or IGF-I.
Mol Cell Endocrinol 1991 Jul
PMID:Effects of gonadotropins, insulin and insulin-like growth factor I on ovarian oxytocin and progesterone production. 166 78

The possible colocalization of oxytocin (OT) and galanin (GAL) was studied by combining, on the same cryostat sections, in situ hybridization (ISH) for OT mRNA with a tritiated oligonucleotide probe and immunohistochemistry (ICC) of GAL. Many cells were either labelled by ISH (OT mRNA containing cells), or by ICC (GAL containing cells). Moreover, some magnocellular neurons in the supraoptic and paraventricular nuclei were labelled for both OT mRNA and GAL. These results demonstrate that some magnocellular neurons of the rat hypothalamus contain both GAL and OT. This approach is suitable for studying the intracellular distribution of OT gene expression and mature GAL under different physiological or experimental conditions.
Brain Res Mol Brain Res 1991 Apr
PMID:Evidence for a colocalization of oxytocin mRNA and galanin in magnocellular hypothalamic neurons: a study combining in situ hybridization and immunohistochemistry. 171 45

Several genomic clones encoding carboxypeptidase-E (CPE) have been isolated and partially sequenced. Southern blot analysis indicates that a single copy of this gene is present in the rat genome. The entire gene spans approximately 50 kilobases and consists of nine exons, each of which contains protein-coding regions. Only one of the exon/intron junctions of the rat CPE gene is present in a comparable position within the genes for carboxypeptidase-A and -B, both of which are only 17-21% homologous to CPE at the amino acid level. Nuclease protection analysis shows that alternative splicing of exons 7, 8, and 9 does not occur, indicating that the heterogeneity of the C-terminal region of CPE is due to posttranslational processing. Primer extension and nuclease protection analyses have identified the 5' end of CPE mRNA to be 105 nucleotides up-stream from the ATG used for protein translation. The 5' flanking region does not contain TATA and/or CCAAT boxes in the near vicinity of the transcription initiation site. The 5' flanking region is GC rich, containing 70% GC residues over nucleotides -1 to -150 (relative to the transcription initiation site). Putative consensus sites for the enhancer elements SP-1, NF-1, Pan-1, and AP-2 are present in the region from -60 to -330. Since this report describes the first neuropeptide-processing enzyme gene to be partially sequenced, it is not possible to compare the sequence with those of other processing enzymes that show similar tissue-specific expression. However, comparison of the CPE sequence with 5' flanking regions of other neuroendocrine genes has revealed a short region (12-18 nucleotides) that is highly conserved among CPE, neuropeptide-Y, oxytocin, insulin, and tyrosine hydroxylase genes.
Mol Endocrinol 1991 Sep
PMID:Structural characterization of the rat carboxypeptidase-E gene. 177 Sep 52

Bovine corpus luteum is the site of intense production of pro-ocytocin-neurophysin mRNA at day 1 after estrus (Ivell et al. (1985) FEBS Lett. 190, 263-267) which is followed by apparent delayed production of ocytocin. Therefore it is a good model to study both the translational and post-translational production of this neuropeptide in non-hypothalamic tissues and its regulation. In order to assess if this mRNA is translated during the lag period we have analyzed the neurophysin-like species produced in this organ. As early as day 2 after estrus one neurophysin species (pI approximately 4.7) could be detected and was unequivocally identified as pro-ocytocin-neurophysin. In primary cultures of luteinizing granulosa cells, biosynthetic intermediates were characterized, i.e. ocytocin-Gly, ocytocin-Gly-Lys and ocytocin-Gly-Lys-Arg, whereas amidated, fully mature, ocytocin was undetectable. We conclude that translation of pro-ocytocin-neurophysin mRNA takes place soon after transcription and we propose that incomplete processing could be responsible for the low level of ocytocin in the early bovine corpus luteum.
Mol Cell Endocrinol 1991 May
PMID:Synthesis and processing of pro-ocytocin in bovine corpus luteum and granulosa cells. 181 98

1. We studied the effects of extracellular sodium on the secretion of vasopressin (VP) and oxytocin (OT) and the efflux of 45Ca from isolated, perfused nerve endings of the rat neurohypophysis (neurosecretosomes). 2. Upon removal of sodium from the perfusing medium, basal release of VP and OT increased by 3.95 +/- 0.23- and 3.71 +/- 0.22-fold, respectively, followed by a decline to about double the levels in normal (150 mM) sodium (P less than or equal to 0.1). 3. Compared to neurosecretosomes perfused in normal (150 mM) sodium, omission of sodium from the medium augmented ionomycin-induced VP and OT secretion by 66 +/- 5- and 20 +/- 3-fold, respectively, and A23187-induced secretion was increased 1.3 +/- 0.4- and 1.3 +/- 0.1-fold (P less than or equal to 0.01 for both ionophores). 4. The inhibition of ionomycin-induced secretion by sodium was concentration dependent (P less than or equal to 0.01 for sodium greater than or equal to 5 mM); the IC50 was about 10 mM sodium for both hormones, and the Hill slope was close to -1. 5. The rate of 45Ca efflux from neurosecretosomes showed 2.7 +/- 0.1-fold stimulation upon increasing sodium from 4.5 to 150 mM (P less than or equal to 0.01). 6. Our results suggest that sodium inhibits basal and stimulated secretion at the nerve terminal, possibly by reducing intraterminal calcium through sodium/calcium exchange.
Cell Mol Neurobiol 1991 Jun
PMID:Sodium inhibits hormone release and stimulates calcium efflux from isolated nerve endings of the rat neurohypophysis. 186 7

Single crystals of a bovine neurophysin II-oxytocin complex have been obtained using (NH4)2SO4 as the precipitating agent. The crystals diffract to at least 2.7 A resolution, belong to Laue group 4/mmm and exhibit systematic absences consistent with either space group P4(1)2(1)2 or P4(3)2(1)2. The cell dimensions are a = b = 69.07 A and c = 113.26 A. The crystals contain one neurophysin-oxytocin dimer per asymmetric unit. Based on a Vm of 2.9 A3/Da, the solvent content is calculated to be 58%. Chromatographic analysis of the dissolved crystals suggests the presence of three oxytocin molecules per neurophysin dimer.
J Mol Biol 1991 Sep 05
PMID:Crystallographic analysis of the neurophysin-oxytocin complex. A preliminary report. 192 Apr 16

Oxytocin and its mRNA have been detected in bovine granulosa cells, but the function of follicular oxytocin is not well understood. We have shown previously that oxytocin exerts a specific, dose-dependent, stimulatory effect on progesterone secretion by granulosa, but not theca cells isolated from bovine preovulatory follicles obtained 48 h after the initiation of luteolysis. The objective of the present study was to characterize the development of granulosa cell responsiveness to oxytocin during the follicular phase. Granulosa cells and theca interna were isolated form preovulatory follicles early in the follicular phase (24 h after the initiation of luteolysis) or after the luteinizing hormone (LH) surge and cultured in defined medium for 5 days with or without oxytocin and in the presence or absence of gonadotropins. Granulosa, but not theca cells obtained before the LH surge increased progesterone production 3.3-fold in response to oxytocin. However, late in the follicular phase, after the LH surge, granulosa cells did not respond to oxytocin (or to follicle-stimulating hormone (FSH) or LH). These findings suggest that the LH surge (1) stimulates granulosa cells to maximal progesterone secretion, so that they cannot be further stimulated, (2) abolishes the responsiveness of granulosa cells to oxytocin, or (3) stimulates granulosa cells to increase oxytocin production, so that exogenous oxytocin has no additional effect.
Mol Cell Endocrinol 1991 Jun
PMID:Oxytocin stimulates progesterone production by bovine granulosa cells isolated before, but not after, the luteinizing hormone surge. 193 22


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