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

Using a recently cloned rat ovary 3 beta-HSD cDNA and antibodies raised against purified human placental 3 beta-HSD, we have studied the effects of treatment with human chorionic gonadotropin (hCG) and hyperprolactinemia achieved by pituitary implants, alone or in combination, on the expression and activity of ovarian 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) in intact adult rats. 32P- and 35S-labeled cDNA probes were used to evaluate the effects of treatments on 3 beta-HSD mRNA levels by dot blot and in situ hybridization, respectively, while enzymatic activity was measured by the conversion of [14C]dehydroepiandrosterone into [14C]androstenedione. The present data show that hCG exerts a marked trophic effect on rat corpora lutea with an increase in total ovarian 3 beta-HSD mRNA levels, 3 beta-HSD protein content as well as enzymatic activity, resulting in an increase in serum progesterone levels. Prolactin-secreting pituitary implants alone, on the other hand, while exerting small effects on 3 beta-HSD expression and activity, led to a marked potentiation of the stimulatory effect of hCG on all parameters. The present data show that hCG and PRL act synergistically to stimulate ovarian progesterone secretion via an increase in 3 beta-HSD mRNA levels, protein content and enzymatic activity.
Mol Cell Endocrinol 1990 Aug 20
PMID:Effects of human chorionic gonadotropin (hCG) and prolactin (PRL) on 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) expression and activity in the rat ovary. 214 42

Rat testicular interstitial cells have been separated by discontinuous/continuous gradient of Percoll, yielding four cell fractions. The light cells in fraction I bound luteinizing hormone/human chorionic gonadotropin (LH/hCG) with high affinity but were not steroidogenic in response to hormone. Fraction II consisted mainly of germ cells. Although fraction III contained Leydig cells, this fraction was contaminated with germ cells and was less responsive to hormone as compared to the Leydig cells in fraction IV. The Leydig cells in fraction IV produced cAMP and testosterone in response to hormone action in a manner which was critically dependent upon cell concentration. The production of cyclic adenosine monophosphate (cAMP) in the presence of saturating concentrations of hCG (2.4 X 10(-10) M) was linear as a function of cell concentration up to 7.0 X 10(6) cells/1.25 ml and thereafter, a slight inhibition (26%) was seen at 10 X 10(6) cells/1.25 ml. The average value for cAMP production by hCG was 133.8 +/- 8.5 pmol cAMP/2 X 10(6) cells. The production of testosterone was biphasic, increasing linearly up to 5 X 10(6) cells/1.25 ml and decreasing thereafter. Two million cells, in the presence of 2.4 X 10(-10) M hCG, produced an average of 24.2 +/- 1.7 ng of testosterone in reaction volumes ranging from 1 to 2 ml whereas the same number of cells only produced 5.1 +/- 0.6 ng of testosterone in 250 microliters. The binding of 125I-labeled hCG to the same batch of cells increased with increasing cell concentrations as expected but under the conditions of maximal steroidogenesis at low cell concentrations (1.25, 2.0, and 2.5 X 10(6) cells/1.25 ml), it was barely detectable. Thus, we conclude that there is an inverse relationship between the parameters of binding and biological response in purified Leydig cells.
Mol Cell Endocrinol 1990 Mar 26
PMID:Gonadotropin receptor occupancy and stimulation of cAMP and testosterone production by purified Leydig cells: critical dependence on cell concentration. 216 Mar 83

Oocytes and matched samples of follicular fluid (FF) were obtained from 70 follicles of five rhesus monkeys stimulated with either pregnant mare serum gonadotropin or human menopausal gonadotropin. Follicular aspiration was performed 30-32 h after human chorionic gonadotropin administration. The concentrations of estradiol (E2), progesterone (P), testosterone (T), and dihydrotestosterone (DHT) in FF were measured. Twenty-six percent of oocytes were classified as mature (M), 41% matured in vitro (Miv), 13% were dysmature, and 20% atretic. M oocytes were associated with significantly higher levels of P and a higher P:E2 ratio. There were no differences in hormone levels associated with fertilized and nonfertilized oocytes. Thirty-five embryos developed to the six- to eight-cell stage in vitro, of which 13 exhibited optimal cleavage rates. Significantly lower levels of E2 and higher P:E2 ratios were associated with the more rapidly cleaving embryos. Proportionally more embryos showing optimal cleavage rates developed from M compared to Miv oocytes, and only embryos derived from M oocytes developed to blastocysts in culture. Optimal cleavage rates to the six- to eight-cell stage in vitro, rather than fertilization rates, are a better indicator of (subsequent) developmental capacity, and, in this study, embryonic development was closely associated with the maturity of the oocyte at recovery.
Mol Reprod Dev 1990 Oct
PMID:Relationships between follicular fluid steroid hormone concentrations, oocyte maturity, in vitro fertilization and embryonic development in the rhesus monkey. 224 77

The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.
J Steroid Biochem Mol Biol 1990 Oct
PMID:Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation. 226 60

Multiple forms of human thyroid hormone (T3) receptor have been identified, including true receptors that bind T3 (alpha 1 and beta) and a splicing variant (alpha 2) that does not bind T3. The alpha 1- and beta-receptors activate transcription through interactions with positive thyroid response elements (TREs). The alpha 2 variant is unable to activate transcription and has been reported to inhibit alpha 1 or beta stimulation of positive TREs, a property referred to as dominant negative activity. In this report we have performed studies to assess the functional properties of different members of the thyroid receptor family with regard to both positive and negative transcriptional regulation. The alpha 1-, alpha 2-, and beta-receptors were each coexpressed in JEG-3 cells with either TreTKCAT (CAT = chloramphenicol acetyltransferase), a reporter gene that contains a positive TRE, or TSH alpha CAT, a negatively regulated reporter gene. The alpha 1 and beta isoforms stimulated transcription of TreTKCAT and inhibited TSH alpha CAT transcription in a T3-dependent manner, whereas the alpha 2 variant was inactive. When coexpressed with alpha 1- or beta-receptors, alpha 2 inhibited regulation of positive TREs, but the effects of alpha 2 were modest and only occurred when relatively high doses of receptor were transfected. The alpha 2-receptor variant did not affect negative regulation by alpha 1- or beta-receptors. Thus, in both positive and negative regulation, thyroid hormone receptor isoforms that bind T3 (alpha 1, beta) are functional, whereas the alpha 2 isoform, which does not bind T3, is not functional.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Oct
PMID:Negative and positive transcriptional regulation by thyroid hormone receptor isoforms. 228

In order to investigate the existence of a chorionic gonadotropin (CG) in the rat, placental mRNA was prepared from either the foetal disc or the maternal site of implantation in pregnant rats and translated in a wheat-germ cell-free translation system in the presence of 35S-labeled methionine and cysteine. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the radioactive material immunoprecipitated using antiserum specific to native rat alpha-subunit allowed us to isolate in translation products from both sources (foetal disc and maternal site of implantation) a single polypeptide of 17 kDa having the electrophoretic properties of the rat pituitary alpha-precursor. This polypeptide was absent in media derived from translation of mRNA extracted from uterine horn of non-pregnant female rats, and was approximately 10 times more abundant when RNA was derived from the maternal part (about 0.25% of cpm in total proteins) rather than the foetal part (0.026%) of the placenta. Immunoprecipitation was prevented in the presence of an excess of rat (but not ovine) alpha-subunit. Antisera directed against denatured bovine alpha-subunit, which cross-react with the rat pituitary alpha-precursor, did not bind the placental peptide. These results suggest that this rat placental polypeptide and the rat alpha-subunit of pituitary glycoprotein hormones have important differences in their primary structure, but share discrete structurally and/or conformationally related regions in their polypeptide chains. The possibility that these partial homologies account for gonadotropin-like activity of a presumed rat CG remains to be ascertained.
Mol Cell Endocrinol 1987 Nov
PMID:Rat placental mRNA directs the synthesis of a polypeptide immunologically related to alpha-subunit of glycoprotein hormones. 244 7

Human chorionic gonadotropin (hCG) beta-subunit core fragment (beta-fragment) is present in the urine of pregnant individuals as well as those with trophoblast disease and certain other cancers at concentrations 0.8 (early pregnancy) to 7 (second trimester pregnancy)-fold greater than that of hCG. The core fragment may be directly secreted by trophoblast tissue into the circulation or possibly originates from peripheral degradation of circulating hormone by the kidney. We examined the former hypothesis. We examined 24-h organ cultures of trophoblast tissue from first, second, and third trimester pregnancy. The media from this tissue contained hCG, free beta-subunit, and beta-fragment. The amount of beta-fragment present exceeded that of hCG, as was observed in second and third trimester pregnancy urine. The beta-fragment immunoreactive material produced by trophoblast tissue was compared to a standard preparation of urinary beta-fragment. The material in medium was identical to the standard beta-fragment in its elution pattern from a gel filtration column, from a reverse-phase HPLC column, from an ion-exchange gel, and from an immobilized lectin affinity column, and also by electrophoresis and immunoblotting with fragment-reactive monoclonal antibodies. We conclude that beta-fragment can also originate directly from trophoblast tissue, and could be the principal hCG beta-immunoreactive molecule secreted.
Mol Endocrinol 1988 Sep
PMID:Origin and occurrence of human chorionic gonadotropin beta-subunit core fragment. 245 7

The alpha and beta subunit genes encoding chorionic gonadotropin (CG) are regulated transcriptionally in placental cells by cyclic AMP (cAMP). The regulatory response sequences of the alpha gene have been studied extensively. Similar studies of the CG beta subunit (CG beta) gene have not been possible because transcriptionally active sequences have not been identified in the clones isolated to date. The CG beta subunit genes form a complex cluster of seven structurally similar genes that include six CG beta-like genes and a single luteinizing hormone beta subunit (LH beta) gene. We isolated overlapping clones containing the entire CG beta/LH beta gene cluster (68 kilobases) from a human genomic cosmid library. The organization of the gene cluster was similar to that found in previous analyses, as determined by Southern blots of genomic DNA, but differed from some of the gene assignments, as determined by fragments cloned in lambda phage. The 5'-flanking sequence of the most active CG beta gene (CG beta 5) was linked to the chloramphenicol acetyltransferase (CAT) coding sequence for analyses of transient expression in different cell types. CG beta CAT was expressed preferentially in JEG-3 choriocarcinoma cells, and expression was markedly stimulated by treatment with 8-bromo-cAMP. Deletion mutagenesis of the CG beta 5'-flanking sequence revealed that multiple regions were required for maximal expression. The kinetics for cAMP stimulation of alpha CAT and CG beta CAT expression were different, suggesting that different pathways may be involved in cAMP-stimulated expression of the alpha and CG beta genes.
Mol Cell Biol 1988 Dec
PMID:Isolation and characterization of the human chorionic gonadotropin beta subunit (CG beta) gene cluster: regulation of transcriptionally active CG beta gene by cyclic AMP. 246 94

The effects of prolactin (PRL), alone and together with human chorionic gonadotropin (hCG), on steroidogenesis and cAMP accumulation in the preovulatory ovary were studied. Cultured granulosa cells obtained from large preovulatory follicles of pregnant mare serum gonadotropin (PMSG)-treated immature rats were used. The results indicated that PRL inhibited, in a dose-dependent manner, hCG-induced cAMP accumulation and 17 beta-estradiol (E2) secretion. When added to 0.4 IU/ml hCG (designated as 100% activity), 1, 10 and 100 ng/ml PRL decreased cAMP accumulation to 86, 64 and 59%, respectively, following 1 h incubation and to 87, 81 and 66% E2 secretion, respectively, following 48 h incubation. PRL alone failed to cause any significant change in cAMP or E2 concentrations. The inhibition of PRL was apparently not at the hCG receptor level, since a similar inhibitory effect was observed in prostaglandin E1 (PGE1)-induced cAMP accumulation. Nor was the inhibitory pathway of adenylate cyclase involved, since pertussis toxin--an inactivator of the Gi regulatory protein--failed to abolish the suppressive effect of PRL on hCG-induced cAMP accumulation. The phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methyl-xanthine, abolished the inhibitory effect of PRL on hCG- and PGE1-induced cAMP accumulation and on hCG-induced E2 secretion, indicating that PRL might be inhibiting cAMP accumulation and steroidogenesis in preovulatory granulosa cells by enhancement of PDE activity.
Mol Cell Endocrinol 1989 Jan
PMID:Prolactin inhibits hCG-stimulated steroidogenesis and cAMP accumulation, possibly by increasing phosphodiesterase activity, in rat granulosa cell cultures. 247 81

In the present work, using an immunological approach, we have investigated the existence of common epitopes between two receptors of the glycoprotein hormone family, lutropin (LH) and thyrotropin (TSH) receptors. We have immunized high responder mice with purified porcine LH receptors obtained by successive affinity chromatographies on agarose-human chorionic gonadotropin (hCG) gels. From one fusion of splenocytes with the murine myeloma NSC1, secreting hybridomas were tested for their anti-LH receptor specificities. During sequential selection for this activity including direct recognition of the purified LH receptors in dot-blot assays and displacement experiments of 125I-pLH and 125I-hCG binding to different sources of receptors, we performed a parallel investigation of their anti-porcine TSH receptor activities. Purified immunoglobulins from two of them showed a TSH-like activity on the iodide metabolism of porcine thyroid cell, this activity being related to the phosphoinositide breakdown pathway; moreover, these antibodies obtained after immunization with porcine LH receptors were able to immunopurify human TSH receptors. The double selection process led us to characterize three groups of immunoglobulins: exclusive specificities for lutropin receptors or thyrotropin receptors and cross-reactive specificities. Our results demonstrate the possibility of sequence homologies at the protein and the gene levels between the receptors for the glycoprotein hormone family supporting the hypothesis of a common origin in evolution.
Mol Cell Endocrinol 1989 Aug
PMID:Lutropin receptor and thyrotropin receptor share a common epitope. 247 48


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