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

The effects of human chorionic gonadotropin (hCG) and prostaglandin F2 alpha (PGF2 alpha) on the adenylate cyclase-cAMP and inositol phospholipid-phospholipase C-inositol trisphosphate and diacylglycerol transmembrane signalling systems were evaluated in cultured human granulosa-luteal cells. Granulosa-luteal cells obtained from patients undergoing in vitro fertilization were cultured for 72 h prior to addition of hormones. During the last 24 h of culture granulosa-luteal cells were incubated with [3H]inositol. Neither hCG nor gonadotropin-releasing hormone (GnRH) stimulated the inositol phospholipid-phospholipase C signalling system. PGF2 alpha stimulated increases in inositol mono-, bis-, and trisphosphate accumulation in 30 min incubations. NaF (20 mM) mimicked the stimulatory effect of PGF2 alpha on inositol phosphate accumulation suggesting the involvement of a guanine nucleotide regulatory protein in the activation of phospholipase C. In contrast, hCG but not PGF2 alpha or NaF stimulated cAMP accumulation in 30 min incubations. Simultaneous treatment with hCG and PGF2 alpha did not alter the stimulatory effect of PGF2 alpha on inositol phosphate accumulation but reduced (37%) the stimulatory effect of hCG on cAMP accumulation. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited the stimulatory effects of hCG (76%) and PGF2 alpha (62%) on cAMP and inositol phosphate accumulation, respectively. Thus, cultures of human granulosa-luteal cells possess multiple transmembrane signalling systems which may be modulated by the activation of protein kinase C.
Mol Cell Endocrinol 1989 Aug
PMID:Effects of human chorionic gonadotropin, prostaglandin F2 alpha and protein kinase C activators on the cyclic AMP and inositol phosphate second messenger systems in cultured human granulosa-luteal cells. 255 Feb 98

The objective of the present studies was to assess whether hormone induction of oocyte maturation in isolated intact follicles may be linked to desensitization of follicle-stimulating hormone (FSH) in the oocyte-cumulus complex (OCC). Incubation of follicles with chorionic gonadotropin (hCG), FSH or epidermal growth factor (EGF) produced a marked inhibition of FSH-dependent cyclic AMP accumulation in OCC with a time-course coincident with the onset of germinal vesicle breakdown (GVBD). These effects were evident within 3 h for both hCG and FSH, but with EGF a reduced response to FSH was seen within 1 h of treatment followed by an increase in GVBD. In contrast, no inhibition of cyclic AMP accumulation was seen in response to cholera toxin, forskolin or LH in OCC derived from follicles incubated with hCG for 3 h. The time-course for induction of oocyte maturation by incubation of the intact follicle with hCG was also coincident with production of prostaglandin (PG) F2 alpha, an indirect marker of cyclooxygenase induction. No effect on metabolic coupling between the oocyte and cumulus cells was seen until 9 h after hCG treatment. Retinoic acid caused a marked decrease in metabolic coupling between the oocyte and cumulus cells but inhibited oocyte maturation both in denuded oocytes and OCC. Since FSH desensitization in OCC, the resumption of meiosis, and production of arachidonic acid-derived products were coincident, it is suggested that abrogation of FSH action in cumulus cells by the ovulatory surge of gonadotropins may initiate oocyte maturation.
Mol Cell Endocrinol 1989 Jul
PMID:Desensitization to follicle-stimulating hormone in cumulus cells is coincident with hormone induction of oocyte maturation in the rat follicle. 255 57

Human chorionic gonadotropin (hCG) behaves as an antagonist upon chemical deglycosylation with hydrogen fluoride. In this study it was found that the alpha- and beta-subunits of deglycosylated hCG (DGhCG) still retained their ability to bind to wheat germ agglutinin (WGA) but not to concanavalin A. The antagonism of DGhCG against activation of adenylate cyclase and steroidogenesis was reversed, when WGA was bound to the N-linked carbohydrate moieties of hCG alpha- and beta-subunits followed by addition of purified Leydig cells. The complex formed by incubation at an approximately equimolar ratio induced the maximal reversal of antagonism. This reversal of antagonism was diminished by addition of N-acetylglucosamine. No increase of steric hindrance at the receptor sites was seen in binding studies of the [125I]DGhCG-WGA complex, indicating that the receptor-binding domain of hCG may not be adjacent to the carbohydrate moieties. Kinetic studies of the hormonal response showed that the DGhCG-WGA complex terminated cAMP accumulation after 30 min of incubation, but not testosterone production. Our results suggest that tetravalent WGA can also reverse the antagonism of DGhCG, as in bivalent antibodies to hCG beta.
Mol Cell Endocrinol 1989 Oct
PMID:Reversal of the antagonism of deglycosylated human chorionic gonadotropin by aggregation with wheat germ agglutinin. 255 27

In order to determine the specific antigenic determinants of human follicle-stimulating hormone (hFSH), hFSH-beta peptides with amino acid residues 33-49 (V2), 95-118 (V3), 76-118 (V3 + 1/2 C2), 1-33 (V1 + C1), 22-33 (1/2C1), and 95-107 (V3 + 1/4C2) according to the nomenclature of Stewart and Stewart [Stewart, M., & Stewart, F. (1977) J. Mol. Biol. 116, 175] as well as additional peptides with the residues 93-107, 91-107, 89-107, 87-107, and 85-107 were chemically synthesized. The peptides were examined in radioimmunoassay systems of FSH, luteinizing hormone (LH), or human chorionic gonadotropin (hCG). V3 + 1/2C2 and V1 + C1 showed immunological activity, whereas the other peptides did not. Antibodies were raised in rabbits against these peptides and examined for specific binding with hFSH, LH, thyroid-stimulating hormone (TSH), and hCG. V3 + 1/2C2 as well as V1 + C1 produced antisera, which specifically bound hFSH, hLH, and hTSH, indicating that the amino acid sequences contained in hFSH-beta peptides V3 + 1/2C2 and V1 + C1 share common antigenic sites with hLH and hTSH. Antisera were produced in rabbits against hFSH-beta, against reduced and S-aminoethylated hFSH-beta (AE-FSH-beta), and against AE-FSH-beta coupled to hemocyanin. Reduced and S-aminoethylated beta-subunit of FSH-beta coupled with hemocyanin produced antisera in rabbits that specifically bound only hFSH and not hLH, hTSH, or hCG.
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PMID:Chemical synthesis of peptide fragments of the hormone-specific beta-subunit of human follicle-stimulating hormone. 258 5

There is little information on the molecular events underlying the effects of cAMP on human chorionic gonadotropin (hCG) and particularly steroidal hormone production in normal trophoblasts. We examined the effects of 8-bromo-cAMP on mRNAs encoding two components of the cholesterol side-chain cleavage system, cytochrome P-450scc and adrenodoxin, and the alpha- and beta-subunits of hCG in cultured cytotrophoblasts. cAMP caused an increase in all of these mRNAs within 24 h, whereas actin mRNA declined. alpha-hCG mRNA increased first, followed by adrenodoxin, beta-hCG and cytochrome P-450scc mRNAs. The effects of 8-bromo-cAMP on alpha- and beta-hCG, adrenodoxin, and cytochrome P-450scc mRNAs, in cytotrophoblasts and JEG-3 choriocarcinoma cells, required the catalytic unit of protein kinases since H-7, a kinase inhibitor, blocked the increase in the mRNAs and prevented the stimulation of hCG and progesterone secretion. 8-Bromo-cAMP promoted a rapid increase in alpha-hCG mRNA in cytotrophoblasts in the presence of cycloheximide, an inhibitor of protein synthesis. In cytotrophoblasts, cycloheximide reduced basal and 8-bromo-cAMP-stimulated adrenodoxin mRNA abundance. In contrast, basal and cAMP-stimulated adrenodoxin mRNA was augmented by cycloheximide in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1989 Jan
PMID:Effects of 8-bromo-cAMP on expression of endocrine functions by cultured human trophoblast cells. Regulation of specific mRNAs. 274 14

The 43 kDa human chorionic gonadotropin (hCG) (SP-hCG) was purified from human placenta and analyzed for sugar moieties. The low hexosamine content suggests that SP-hCG probably lacks O-linked sugar chains in the beta-subunit and incompletely formed N-linked sugar chains in the alpha- and beta-subunits. In the present study SP-hCG was hydrolyzed with various glycosidases. Treatment of hCG or SP-hCG with O-glycan peptide hydrolase increased the mobility of asialo-hCG beta in reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) while that of SP-hCG beta was unaffected, indicating that SP-hCG beta does not contain NeuNAc-Gal-GalNAc unit. Alpha-Mannosidase and endoglycosidase H hydrolyzed mannose and the high mannose-GlcNAc moieties, respectively, from alpha- and beta-subunits of SP-hCG, but not from the subunits of authentic hCG. Glycopeptidase F hydrolyzed completely the N-linked sugar chains from SP-hCG subunits, producing alpha- and beta-subunits with estimated Mr of 15,000 and 18,500, respectively. The biological activity of purified SP-hCG is about 50-80% of highly purified authentic hCG. In an in vitro system SP-hCG increased cAMP accumulation and testosterone production by rat Leydig cells to the same levels as that induced by hCG. However, the biological activity of SP-hCG was markedly reduced, following treatment with endoglycosidase H or alpha-mannosidase. To attain the level of testosterone production equivalent to that induced with untreated SP-hCG, 10-20 times higher dose of treated SP-hCG was required. On the other hand, cAMP accumulation induced with treated SP-hCG even at a very high concentration was substantially lower than that attained with untreated SP-hCG. In conclusion, the mannose moieties are essential structural components of the hormone in stimulating cAMP accumulation and steroidogenesis by rat Leydig cells.
Mol Cell Endocrinol 1989 Mar
PMID:Carbohydrate moieties of small placental hCG: requirement of mannose structure for biological activity. 274 19

The alpha subunit of the placental hormone chorionic gonadotropin is regulated by cyclic AMP (cAMP) at the transcriptional level. A cAMP-responsive fusion gene (alpha-CAT) containing 1.5 kilobases of the alpha gene 5'-flanking sequence linked to the chloramphenicol acetyltransferase (CAT) gene was used as a transcriptional reporter in competition assays in transfected JEG-3 choriocarcinoma cells. Expression of the alpha-CAT fusion gene increased linearly with increasing amounts of transfected plasmid and was maximal at the same amount of alpha-CAT DNA (2 micrograms) with or without cAMP treatment. Various amounts of different competitor DNA sequences were cotransfected with the alpha-CAT reporter plasmid to examine the interactions of intracellular trans-acting factors with the regulatory elements of the alpha gene promoter. An 800-base-pair fragment of alpha gene 5'-flanking sequence inhibited both basal and cAMP-stimulated transcription of the alpha-CAT reporter plasmid in a dose-dependent manner, indicative of interactions with one or more trans-acting factors that activate alpha gene expression. The alpha gene sequences that interact with intracellular regulatory factors were defined by using several discrete regions of the 5'-flanking sequence as competitors for alpha-CAT expression. A proximal promoter sequence (-99 to +44) containing the CCAAT box, TATA box, and transcriptional initiation site was a relatively ineffective competitor of alpha-CAT transcription. In contrast, an upstream sequence between -236 and -100 was an effective competitor for transcriptional activators of alpha-CAT expression. Competition for alpha-CAT expression by this regulatory sequence did not require cis interactions with downstream promoter elements and was equally effective with or without cAMP treatment. An 18-base-pair repeated sequence within this region of the alpha gene (-146 to -111) greatly enhanced both basal gene expression and cAMP responsivity and also competed for limiting cellular transcription factors. These findings suggest that JEG-3 cells contain trans-acting factors that interact with a cAMP response element to activate alpha gene transcription. The chorionic gonadotropin beta gene 5'-flanking sequence also competed for alpha-CAT expression, suggesting that a common trans-acting factor is shared by the regulatory sequences of the alpha and beta genes.
Mol Cell Biol 1987 Sep
PMID:trans-acting factors interact with a cyclic AMP response element to modulate expression of the human gonadotropin alpha gene. 282 16

Alterations of the cytoplasmic domain of the vesicular stomatitis virus glycoprotein (G protein) were shown previously to affect transport of the protein from the endoplasmic reticulum, and recent studies have shown that this occurs without detectable effects on G protein folding and trimerization (R. W. Doms et al., J. Cell Biol., in press). Deletions within this domain slowed exit of the mutant proteins from the endoplasmic reticulum, and replacement of this domain with a foreign 12-amino-acid sequence blocked all transport out of the endoplasmic reticulum. To extend these studies, we determined whether such effects of cytoplasmic domain changes were transferable to other proteins. Three different assays showed that the effects of the mutations on transport of two membrane-anchored secretory proteins were the same as those observed with vesicular stomatitis virus G protein. In addition, possible effects on oligomerization were examined for both transported and nontransported forms of membrane-anchored human chorionic gonadotropin-alpha. These membrane-anchored forms, like the nonanchored human chorionic gonadotropin-alpha, had sedimentation coefficients consistent with a monomeric structure. Taken together, our results provide strong evidence that these cytoplasmic mutations affect transport by affecting interactions at or near the cytoplasmic side of the membrane.
Mol Cell Biol 1988 Jul
PMID:Effects of altered cytoplasmic domains on transport of the vesicular stomatitis virus glycoprotein are transferable to other proteins. 284 89

The effects of inhibitors of pregnenolone metabolism, WIN-24540 and spironolactone, on adrenocorticotropic hormone (ACTH)- and human chorionic gonadotropin (hCG)-induced cAMP and steroid production by bovine (BAC) and ovine (OAC) adrenal cells and pig Leydig cells (PLC) were investigated. The inhibitors reduced cAMP production by adrenal and Leydig cells by about 75% and 60%, respectively (P less than 0.001). Further, the inhibitors also reduced the cholera toxin- and forskolin-induced cAMP production by pig Leydig cells. In the presence of the inhibitors, corticosterone and testosterone production by BAC and PLC, respectively, following hormonal stimulation was reduced by more than 90%. However, pregnenolone production by BAC and PLC under these conditions represented only 12% and 42% of the corticosterone and testosterone production, respectively, in the absence of inhibitors. Moreover, the inhibitors also reduced the steroidogenic response of PLC to 8-Br-cAMP and the conversion of 22(R)-hydroxycholesterol to pregnenolone by BAC and PLC. The reduced production of pregnenolone in the presence of inhibitors was in part due to the weak inhibition of 17 alpha-hydroxylase by spironolactone. However, when OAC cells were incubated in the presence of WIN-24540 and SU-10603, a potent 17 alpha-hydroxylase inhibitor, the amount of pregnenolone produced in response to ACTH or 22(R)-hydroxycholesterol was only 10% and 19%, respectively, of the steroids (corticosterone plus cortisol) secreted in the absence of inhibitors. The results show that the inhibitors of pregnenolone metabolism reduced, in both adrenal and Leydig cells, the response of adenylate cyclase to several effectors and the activity of the cholesterol side-chain cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 Nov
PMID:Inhibition of hormonal-induced cAMP and steroid production by inhibitors of pregnenolone metabolism in adrenal and Leydig cells. 285 Sep 48

In pregnant mare serum gonadotropin treated immature rats hypophysectomized on the day of ovulation (day 1) the corpora lutea (CL) persist as normal morphological structures and produce steroids, especially 20 alpha-dihydroprogesterone (20 alpha-DHP), for at least 40 days (Taya and Greenwald, 1982), although there is a rapid decline in human chorionic gonadotropin (hCG) binding sites (Kim and Greenwald, 1984). In this study the number of occupied and non-occupied hCG receptors in CL from hypophysectomized rats decreased to 14% and 36%, respectively, compared to intact day 5 pseudopregnant animals, but the binding affinity was unchanged. Decreased concentration of occupied hCG receptors paralleled hormonal levels of serum luteinizing hormone (LH) which were measurable in only 9 out of 20 animals and were near the lower limits of the assay (40 pg/ml). Luteal progesterone (P4) production in response to LH was markedly decreased after hypophysectomy, but the maximal P4 response to LH and 20 alpha-DHP production in response to LH and 8-Br-cAMP were the same in hypophysectomized and intact animals. Although hCG receptor concentration in CL decreased significantly after hypophysectomy, LH-stimulated luteal production of cAMP was almost the same in both groups. These results indicate that LH spare receptors which are uncoupled from cAMP exist in the CL of the intact pseudopregnant rat and that after hypophysectomy they quickly disappear within 4 days.
Mol Cell Endocrinol 1985 May
PMID:Evidence for rapid loss of spare hCG receptors in the corpora lutea of the hypophysectomized rat. 298 28


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