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

We have examined the effects of steroidogenesis-inducing protein (SIP), previously isolated from human follicular fluid, on the synthesis of DNA by granulosa cells isolated from diethylstilbestrol-primed immature rats. SIP alone had no effect but in conjunction with transforming growth factor-beta (TGF-beta) there was an increase in [3H]thymidine incorporation into granulosa cell DNA. The increase in [3H]thymidine into DNA was due to an increase in the number of labeled granulosa cells as assessed by autoradiography. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) interfered with the ability of SIP and TGF-beta to promote DNA synthesis. Previously, we reported that the growth-promoting action of follicle-stimulating hormone (FSH) on rat granulosa cells in vitro was dependent on TGF-beta, and EGF inhibited the actions of FSH plus TGF-beta on [3H]thymidine incorporation into DNA. Since the dependency of SIP on its interactions with TGF-beta and the ability of EGF to interfere with the process were similar to the properties reported for FSH, this raised the possibility that the actions of SIP were mediated through the accumulation of intracellular cAMP. However, when the hypothesis was tested, SIP had no effect on cAMP levels in the presence or absence of TGF-beta, under conditions in which FSH stimulated cAMP accumulation. In conclusion, DNA synthesis in rat granulosa cells is dependent on the presence of TGF-beta. In the presence of TGF-beta, FSH or SIP, acting through cAMP-dependent and cAMP-independent mechanisms respectively, can recruit more cells to enter the cell cycle and initiate DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Nov
PMID:Steroidogenesis-inducing protein interacts with transforming growth factor-beta to stimulate DNA synthesis in rat granulosa cells. 128 92

Regulation of androgen receptor (AR) mRNA expression was studied in Sertoli cells and peritubular myoid cells isolated from immature rat testis, and in the lymph node carcinoma cell line derived from a human prostate (LNCaP). Addition of dibutyryl-cyclic AMP (dbcAMP) to Sertoli cell cultures resulted in a rapid transient decrease in AR mRNA expression (5 h), which was followed by a gradual increase in AR mRNA expression (24-72 h). This effect of dbcAMP mimicked follicle-stimulating hormone (FSH) action. In peritubular myoid cells, there was only a moderate but prolonged decrease during incubation in the presence of dbcAMP, and in LNCaP cells no effect of dbcAMP on AR mRNA expression was observed. When Sertoli cells or peritubular myoid cells were cultured in the presence of androgens, AR mRNA expression in these cell types did not change. This is in contrast to LNCaP cells, that showed a marked reduction of AR mRNA expression during androgen treatment. In the present experiments, transcriptional regulation of AR gene expression in Sertoli cells and LNCaP cells was also examined. Freshly isolated Sertoli cell clusters were transfected with a series of luciferase reporter gene constructs, driven by the AR promoter. It was found that addition of dbcAMP to the transfected Sertoli cells resulted in a small but consistent increase in reporter gene expression (which was interpreted as resulting from AR promoter activity); a construct that only contained the AR 5' untranslated region of the cDNA sequence did not show such a regulation. The same constructs, transfected into LNCaP cells, did not show any transcriptional down-regulation when the synthetic androgen R1881 was added to the cell cultures. A nuclear transcription elongation experiment (run-on), however, demonstrated that androgen-induced AR mRNA down-regulation in LNCaP cells resulted from an inhibition of AR gene transcription. The present results indicate that in Sertoli cells and LNCaP cells, hormonal effects on AR gene transcription play a role in regulation of AR expression. However, AR gene transcription in these cells is differentially regulated.
Mol Cell Endocrinol 1992 Oct
PMID:Transcriptional regulation of androgen receptor gene expression in Sertoli cells and other cell types. 133 8

c-Fos and c-jun are immediate early proto-oncogenes encoding proteins for the heterodimer AP-1, a DNA binding complex which regulates gene transcription. In order to investigate the presence and potential gonadotropin regulation of mRNAs for these proto-oncogenes in rat granulosa cells, we used Northern blotting of total RNA from cultured cells. Granulosa cells obtained from diethylstilbestrol (DES)-treated weanling rats were challenged with follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), dibutyryl cAMP ((Bu)2cAMP) or tetradecanoyl-13-phorbol acetate (TPA) either 2.5 h after cell isolation (day 0) or following a 2-day pretreatment with FSH (day 2). Freshly isolated cells treated with FSH exhibited 4-fold and 3-fold increases in c-fos and c-jun mRNAs, respectively, within 30 min. Two hours after FSH treatment, both c-fos and c-jun message levels diminished to near control levels. Granulosa cells pretreated for 2 days with FSH, then re-challenged with FSH, showed similar increases in both c-fos and c-jun messages. These effects were dose- and time-dependent on both day 0 and day 2. Likewise, (Bu)2cAMP also increased c-fos and c-jun mRNAs in a time- and dose-dependent manner on both day 0 and day 2. In contrast, LH or hCG minimally increased c-fos and c-jun mRNAs on day 0, but on day 2, both hormones markedly increased message levels in a manner similar to that seen with FSH. Analogous effects were observed with TPA which minimally stimulated c-fos and c-jun mRNAs on day 0, but markedly increased these messages on day 2. These studies demonstrate that c-fos and c-jun mRNAs can be induced in cultured rat granulosa cells by acute gonadotropin, (Bu)2cAMP or phorbol ester treatment and suggest that these immediate early proto-oncogenes may play a role in granulosa cell function.
Mol Cell Endocrinol 1992 Dec
PMID:Gonadotropin regulation of c-fos and c-jun messenger ribonucleic acids in cultured rat granulosa cells. 133 29

Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the male rat and monkey. In the present study we examined the effect of EAAs on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In ovariectomized immature female rats N-methyl-D-aspartate (NMDA) inhibited LH but not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated LH but not FSH secretion when administered on proestrus to adult female rats. Both glutamate and kainate were also found to stimulate LH but not FSH secretion in estrogen-treated ovariectomized immature rats. This study suggests that EAA neurotransmission may be an important component in the expression of gonadotropin surges and that EAA effects appear to be subject to gonadal steroid regulation.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid hormones. 134 28

Testes from adult (90-120-day-old) rats, which had been made cryptorchid 28 days previously, were dispersed by successive treatment with trypsin, collagenase and hyaluronidase. The resulting crude cell suspension was fractionated on discontinuous Percoll density gradients to yield five distinct cell bands (1-5), at the interface between successive layers of Percoll. Crude cells and purified fractions were cultured for up to 7 days, and inhibin was subsequently measured in the media by radioimmunoassay and in vitro bioassay. Sertoli cells from density gradient bands 2 (1.03-1.04 g/ml) and 3 (1.04-1.05 g/ml) showed minimal germ cell or peritubular cell contamination, as determined by morphological and histochemical techniques. Cells from these bands secreted significantly higher levels of immunoactive inhibin/microgram DNA/48 h under both basal and either follicle-stimulating hormone (FSH)- (100 ng/ml) or dibutyryl cAMP-stimulated (100 micrograms/ml) conditions than did cells from the other bands. While there was a decline in basal secretion of inhibin with increasing duration of culture, the capacity of the purified Sertoli cells (bands 2 and 3) to respond to both FSH and dibutyryl cAMP increased over the culture period. The addition of dibutyryl cAMP (31.25-500 micrograms/ml) to the purified Sertoli cells also caused a stimulation of bioactive inhibin. Immunoactive inhibin production by purified Sertoli cells was unaffected by the addition of either rat LH (8 ng/ml) or testosterone (10(-6) M). The data describe a method for the isolation of adult Sertoli cells from cryptorchid testes, and demonstrate their responsiveness to both FSH and dibutyryl cAMP in vitro using the measurement of immunoactive inhibin as a marker of Sertoli cell function.
Mol Cell Endocrinol 1992 Sep
PMID:Characterisation of adult Sertoli cell cultures from cryptorchid rats: inhibin secretion in response to follicle-stimulating hormone stimulation. 135 83

Calcium-dependent transglutaminase (TGase) activity, determined by incorporation of [1,4-14C]diaminobutane dihydrochloride (putrescine) into casein, was demonstrated in a light membrane fraction prepared from bovine calf testicular homogenates. Purification of these membranes by sucrose density gradient centrifugation produced a follicle-stimulating hormone (FSH) receptor-enriched fraction containing TGase activity which cosolubilized with the FSH receptor and could be incorporated with detergent-solubilized receptor into liposomes. In the present study, we show that calcium increases specific binding of FSH to receptor in a concentration-related manner, and is associated with an increase (13.2-fold at 20 mM) in the affinity (Ka) of the receptor with no significant (P greater than 0.05) change in receptor concentration. Treatment of the light membrane fraction with monodansylcadaverine (MDC, 1 mM), a specific inhibitor of TGase, did not affect specific binding of FSH, but resulted in only a 3.9-fold increase in Ka at 20 mM calcium with no change in receptor concentration. Specific binding of FSH to receptor at 4 degrees C was also enhanced by calcium. Scatchard analysis of competitive binding inhibition data showed a Ka at 20 mM calcium similar to that observed with MDC. Dissociation of [125I]hFSH-receptor complexes formed at 30 degrees C in the presence of calcium was significantly less than dissociation of complexes formed at 30 degrees C in the absence of calcium. When [125I]hFSH-receptor complexes were formed at 30 degrees C in the presence of calcium and dissociated in calcium-deficient buffer, dissociation increased 3-fold. Similar results were obtained in the presence of MDC.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Sep
PMID:Stabilization of follicle-stimulating hormone-receptor complexes may involve calcium-dependent transglutaminase activation. 135 84

In this study we investigated the involvement of several different pituitary hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized (hypox) at 19 days of age were supplemented with highly purified human prolactin (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady-state mRNAs levels of the following genes in the prostate: androgen receptor (AR) (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold), and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative effects on these parameters. To test whether the enhancing effect of PRL and GH on AR-mRNA abundance was followed by increased content in the protein itself, binding assays were performed with the androgen agonist [3H]R1881 (131 and 153 fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition to the well-documented presence of prolactin receptors in prostatic tissues, we have further demonstrated, by means of nuclease S1 protection assays plus dot- and Northern-blot analyses, that a GH receptor mRNA is produced in the immature rat prostate. Moreover, we observed not only strong lactogenic but also purely somatogenic binding to be occurring in the immature prostates. Finally, we have studied IGF-I mRNA content in separated epithelial/stromal cell fractions and have concluded that IGF-I expression is principally located in the prostatic stroma. Taken together, these results suggest that PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development.
Mol Cell Endocrinol 1992 Oct
PMID:Growth hormone and prolactin stimulate androgen receptor, insulin-like growth factor-I (IGF-I) and IGF-I receptor levels in the prostate of immature rats. 136 Sep 28

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.
Mol Cell Biol 1992 May
PMID:Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein. 137 9

The modulation of FSH secretion at the beginning and middle of the follicular phase of the cycle represents the key event in the growth and selection of the preovulatory follicle. However, the mechanisms that operate within the pituitary gland to control the increased release of FSH and its subsequent inhibition in vivo remain unclear. Treatment of ewes with bovine follicular fluid (bFF) during the luteal phase has been previously shown to suppress the plasma concentrations of FSH and, following cessation of treatment on day 11, a rebound release of FSH occurs on days 12 and 13. When luteal regression is induced on day 12, this hypersecretion of FSH results in an increase in follicle growth and ovulation rate. To investigate the mechanisms involved in the control of FSH secretion, ewes were treated with twice daily s.c. injections of 5 ml bFF on days 3-11 of the oestrous cycle and luteal regression was induced on day 12 with prostaglandin (PG). The treated ewes and their controls were then killed on day 11 (luteal), or 16 or 32 h after PG and their pituitaries removed and halved. One half was analysed for gonadotrophin and gonadotrophin-releasing hormone (GnRH) receptor content. Total pituitary RNA was extracted from the other half and subjected to Northern analysis using probes for FSH-beta, LH-beta and common alpha subunit. Frequent blood samples were taken and assayed for gonadotrophins. FSH secretion was significantly (P less than 0.01) reduced during bFF treatment throughout the luteal phase and then significantly (P less than 0.01) increased after cessation of treatment, with maximum secretion being reached 18-22h after PG, and then declining towards control values by 32h after PG. A similar pattern of LH secretion was seen after bFF treatment. Pituitary FSH content was significantly (P less than 0.05) reduced by bFF treatment at all stages of the cycle. No difference in the pituitary LH content was seen. The increase in GnRH receptor content after PG in the controls was delayed in the treated animals. Analysis of pituitary mRNA levels revealed that bFF treatment significantly (P less than 0.01) reduced FSH-beta mRNA levels in the luteal phase. Increased levels of FSH-beta, LH-beta and alpha subunit mRNA were seen 16h after PG in the bFF-treated animals, at the time when FSH and LH secretion from the pituitary was near maximum.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1992 Apr
PMID:Relationship between gonadotrophin subunit gene expression, gonadotrophin-releasing hormone receptor content and pituitary and plasma gonadotrophin concentrations during the rebound release of FSH after treatment of ewes with bovine follicular fluid during the luteal phase of the cycle. 138 Nov 79

The purpose of this study was to identify peptide sequences of human follicle-stimulating hormone-beta (hFSH beta) which are accessible subsequent to association with hFSH alpha in heterodimeric hFSH. Antisera were raised against synthetic peptides (Abpep) corresponding to hFSH beta sequences 1-20, 16-36, 33-53, 49-67, 66-85, 81-100 and 98-111. The topography of hFSH beta was studied by testing the binding of these antisera to hFSH beta and hFSH captured by monoclonal antibodies (MAb) in an enzyme-linked immunosorbent assay (ELISA). When hFSH and hFSH beta were captured by the same MAb, binding of Ab16-36, Ab33-53, Ab81-100 and Ab98-111 to hFSH was significantly lower compared to hFSH beta. However, compared to other Abpep, binding of Ab35-53 to hFSH was strong. Similar results were obtained when hFSH was captured by an alpha-specific MAb (10.3A6). Using 10.3A6, it was also possible to demonstrate significant binding of Ab49-67 to hFSH. The data suggests that residues in regions 33-53 and 49-67 of hFSH beta appear to be accessible in the heterodimeric hFSH in addition to the glycosylated region of 1-15. Regions 16-36, 33-53, 81-100 and 98-111 of hFSH beta appear to contain subunit contact-associated sequences which are either masked or structurally altered subsequent to association with hFSH alpha in the heterodimeric hFSH.
Mol Cell Endocrinol 1992 May
PMID:Topographic analysis of human follicle-stimulating hormone-beta using anti-peptide antisera. 138 28


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