Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal peptide (VIP) was originally isolated from porcine duodenum and considered to be a gut hormone. Recent evidence indicates that it may also be involved in reproductive functions. In this study, a possible action of VIP on steroidogenesis by cultured testicular cells was investigated. Neonatal testicular cells were treated in vitro with hormones for 3 days and medium steroid or cAMP content was measured by radioimmunoassay. Treatment of cultured cells with VIP (10(-9) to 10(-6) M) increased the production of testosterone, progesterone, and pregnenolone in a dose-dependent fashion. Testosterone production in response to 10(-6) M VIP was about 5-10% of that maximally induced by LH. Addition of methyl-isobutyl-xanthine, a phosphodiesterase inhibitor, to the VIP-containing cultures significantly enhanced production of testosterone by 13-fold, of progesterone by 9-fold, and of pregnenolone by 2.5-fold as compared to treatment with VIP alone. Additional experiments also showed a dose-dependent stimulation of cAMP production by VIP. The VIP-related hormones PHM-27, secretin, and glucagon also stimulated progesterone and testosterone production with a potency order (PHM-27 greater than secretin greater than glucagon) consistent with that observed for other VIP receptor-mediated actions. A direct stimulatory effect of VIP on Leydig cells was indicated in studies on steroidogenesis by testicular cells separated on a metrizamide density gradient. In these studies, VIP stimulated androgen production in an LH-responsive subpopulation of testis cells but failed to affect steroid production in non-LH-responsive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1986 Nov
PMID:Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells. 243 Aug 45

The ductus deferens smooth muscle tumor cell line (DDT1-MF-2) is very sensitive to steroids. Treatment with 10 nM testosterone accelerates the growth of DDT1 cells in the absence of serum. Glucocorticoids in the presence or absence of androgens inhibits growth. Stimulation of growth of DDT1 cells by testosterone can be replaced by the addition of heparin-binding growth factor I and II (HBGF). Addition of testosterone plus HBGF growth factors results in a further increase in cell number. By in situ hybridization, accumulation of HBGF-I mRNA is significantly increased by testosterone treatment of low density cultures. Testosterone treatment of high density cultures results in no stimulation of HBGF-I mRNA accumulation. Glucocorticoids alone, which block growth of DDT1 cells, have no effect of HBGF-I mRNA accumulation. However, the simultaneous addition of glucocorticoid and androgens to DDT1 cells results in a rapid accumulation of HBGF-I mRNA by 12 h, although growth is inhibited by the presence of both steroid analogs.
Mol Endocrinol 1989 Nov
PMID:Androgens and glucocorticoids modulate heparin-binding growth factor I mRNA accumulation in DDT1 cells as analyzed by in situ hybridization. 248 16

Follicle-stimulating hormone (FSH) and testosterone stimulate the production of a variety of proteins by immature Sertoli cells. A highly purified Sertoli cell preparation was incubated for 3 days with FSH and testosterone. Both androgen receptor protein and mRNA concentrations were markedly increased by FSH. Testosterone also increased the androgen receptor protein concentration, but did not increase the expression of the androgen receptor mRNA. It is concluded that FSH plays a role in the responsiveness of Sertoli cells to testosterone.
Mol Cell Endocrinol 1989 May
PMID:Follicle-stimulating hormone regulates androgen receptor mRNA in Sertoli cells. 250 58

The testicular paracrine factor PModS is produced by peritubular myoid cells under androgen control and modulates Sertoli cell function and differentiation. The observation that luteinizing hormone (LH) stimulates inhibin production in vivo, but has no effect on isolated Sertoli cells in vitro, suggested an indirect mode of LH action, potentially mediated by PModS. The effects of the testicular paracrine factor PModS and hormones on inhibin secretion by Sertoli cells were investigated to provide insight into the endocrine control of inhibin expression. An inhibin radioimmunoassay was utilized which showed essentially parallel displacement curves with purified bovine follicular fluid inhibin, Sertoli cell conditioned medium and concentrated Sertoli cell secreted proteins. An immunoblot analysis of Sertoli cell secreted proteins with the inhibin antisera consistently detected a 32 kDa protein which is the expected size of the mature of inhibin (alpha beta) and periodically detected a 57 kDa protein which is speculated to be an incomplete processed form of the inhibin precursor (alpha 43 beta). Follicle-stimulating hormone (FSH) was found to stimulate inhibin secretion initially between days 2 and 5 of Sertoli cell culture. Insulin and retinol alone had no significant effect on inhibin secretion; however, together they appeared to enhance the ability of FSH to stimulate inhibin secretion. Testosterone had no effect on inhibin production alone or in combination with other regulatory agents. PModS was found to stimulate inhibin secretion approximately 3-fold, but with a delayed time course of stimulation which did not occur until days 5-7 of Sertoli cell culture. Treatment with a combination of PModS and FSH resulted in an apparent maximal stimulation of inhibin secretion. Both forms of PModS, PModS (A) and PModS (B), were found to have equivalent biological activities in their ability to stimulate inhibin production with an apparent half-maximal effective concentration between 10 and 15 ng/ml. The current study provides evidence for the local testicular control of inhibin production and adds to the complexity of the endocrine control of inhibin expression. The cellular interaction is proposed in which LH acts on Leydig cells to stimulate androgen production which in turn acts on peritubular cells to regulate PModS production which subsequently can act on Sertoli cells to control inhibin production. Testicular control of inhibin production provides a potential short feedback loop for the local regulation of androgen production and an additional regulatory element for the pituitary-gonadal axis.
Mol Cell Endocrinol 1989 Oct
PMID:Stimulation of Sertoli cell inhibin secretion by the testicular paracrine factor PModS. 251 83

The effect of castration and gonadal steroid replacement on the concentrations of LH-beta and alpha subunit and prolactin mRNA was examined in mice. Mouse LH-beta, alpha and prolactin mRNAs were approximately 0.8, 0.7 and 1.1 kb in size respectively. After ovariectomy, LH-beta mRNA levels increased 2- to 2.5-fold, while alpha mRNA levels increased 2.5-fold 6 and 10 days after ovariectomy. Serum LH rose after 2 days to reach six times control values at 10 days. Pituitary LH content doubled by 8 days after ovariectomy. Prolactin mRNA levels decreased to 50-60% of control at 3, 6, 8 and 10 days after ovariectomy and parallelled the fall in serum prolactin. Pituitary prolactin content fell more slowly, to 50% of intact control values by 10 days. The increase in both LH-beta and alpha subunit mRNA, and decrease in prolactin mRNA, and serum and pituitary hormone changes, after ovariectomy were prevented by oestradiol or oestradiol plus progesterone replacement. Levels of LH-beta mRNA increased more quickly in male than in female mice, the earliest change being seen 24 h after orchidectomy. Maximum values (two- to threefold) were found on day 6 after orchidectomy. Concentrations of alpha mRNA increased by 12 h to between 2 and 2.5 times control from 3 to 10 days after orchidectomy. Serum LH doubled by 12 h and was three to five times greater than control values up to 10 days. Pituitary LH content fell by 48 h before gradually increasing to intact values after 10 days. Prolactin mRNA levels decreased progressively from 2 days after orchidectomy, and this decrease was preceded by a fall in serum and pituitary prolactin which remained low throughout the experiment. Testosterone treatment attenuated the rise in alpha mRNA, prevented the rise in LH-beta mRNA and serum LH and partially restored the decrease in prolactin mRNA seen after orchidectomy. We conclude that in mice, as in rats and ewes, both LH-beta and alpha subunit mRNAs are negatively regulated by gonadal steroids, whereas prolactin mRNA is positively regulated, although there are temporal differences in patterns of mRNA responses between males and females. By comparison with female rats the rise in LH-beta mRNA after ovariectomy was slower in mice. Moreover, the discordant changes in pituitary LH content and LH subunit mRNAs seen in mice after castration were not observed in rats. Furthermore, pituitary prolactin and prolactin mRNA do not fall after orchidectomy of rats.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1989 May
PMID:Regulation of LH subunit and prolactin mRNA by gonadal hormones in mice. 275 30

Using methods for cell lysis and fractionation which yield essentially quantitative recovery of rat prostate cancer cell cytosolic and nuclear androgen receptors, we examined androgen modulation of androgen receptor content of clonally derived prostate cancer cell lines. We showed that testosterone elicited a concentration-dependent 2.3-fold increase in T5 cell androgen receptor content which was maximum after 48 h and was maintained through at least 72 h of culture. Testosterone caused only a 1.4-fold elevation in D2 cell androgen receptor content which was maximum between 6 and 12 h of culture and was maintained through at least 72 h culture. In contrast, testosterone did not cause a change in C3 cell androgen receptor content. Cycloheximide inhibition showed that both the testosterone-mediated increase in and maintenance of basal prostate cancer cell androgen receptor content required protein synthesis. Because testosterone and the nonmetabolizable androgen R1881 were essentially equipotent as effectors of the increase in T5 cell androgen receptor content, findings using testosterone appear to represent maximum effects. RU 23908 antagonized both R1881 and testosterone promoted elevations of prostate cancer cell androgen receptor content. Effectiveness of RU 23908 was comparable to the relative binding affinity of R1881, testosterone and RU 23908 for androgen receptors. This implies that at least part of the androgen-promoted increase in prostate cancer cell androgen receptor content is mediated through the action of androgen receptors and suggests that androgen receptors may act as both cis and trans regulatory elements. The mechanisms which determine basal or androgen-modulated prostate cancer cell androgen receptor content remain to be elucidated.
Mol Cell Endocrinol 1989 May
PMID:Androgen modulation of prostate cancer cell androgen receptor content is cell line specific. 278 64

Gonadotropin-releasing hormone (GnRH) has specific receptor sites in rat Leydig cells and has direct effects on their steroidogenesis. The purpose of the present study was to examine whether activation of the calcium- and phospholipid-dependent protein kinase C (PK-C) is involved in GnRH effects on rat Leydig cells, as has been shown in pituitary gonadotrophs. Testosterone production of Percoll-purified Leydig cells was similarly stimulated (about 50-100%) by a GnRH agonist (buserelin, maximum effect at concentration of 10(-9) mol/l and above) and a tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, maximum effect at 10(-8) mol/l), which is known to activate PK-C. In contrast, a GnRH antagonist (10(-5) mol/l) and an inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate (10(-6) mol/l), were without effect on testosterone. None of these substances had clear effects on cAMP production. The maximum steroidogenic effects of GnRH agonist and TPA were the same whether used separately or together, suggesting that they share a common mechanism of action. TPA translocated the cytosolic proportion of Leydig cell PK-C activity to a membrane-associated form almost instantaneously, within 0.5-1 min. A similar translocation, though less complete, was observed in the presence of buserelin in 1-4 min. Inclusion of a 100-fold excess of a potent GnRH antagonist completely prevented the translocation of PK-C. These results provide evidence that GnRH agonist activates PK-C also in the testis tissue, and this may be the mechanism whereby it affects Leydig cell endocrine function.
Mol Cell Endocrinol 1988 Jan
PMID:Gonadotropin-releasing hormone agonist activates protein kinase C in rat Leydig cells. 283 41

The objective of the present studies was to evaluate and compare the effects of 5 alpha-dihydrotestosterone (DHT) to those of 2-hydroxyestradiol (2-OH-E2) and 2-methoxyestradiol (2-MeO-E2) on progesterone production in cultured porcine granulosa cells. Granulosa cells were exposed to various treatments of DHT, 2-OH-E2 and 2-MeO-E2 in the absence or presence of follicle stimulating hormone (FSH) for 4 days and concentrations of progesterone in medium and cell numbers were determined. In the absence of FSH, maximally effective concentrations of DHT (1 micrograms/ml) and 2-OH-E2 (4 micrograms/ml) stimulated progesterone production (ng/10(5) cells/48 h) to 2.2 +/- 0.2- and 10.8 +/- 2.2-fold of controls (n = 4 experiments), respectively. In the presence of 200 ng/ml FSH, progesterone production stimulated by 1 micrograms/ml DHT and 4 micrograms/ml 2-OH-E2 was 5.4 +/- 1.1- and 15.5 +/- 6.0-fold of controls (n = 4 experiments), respectively. Thus, FSH appeared to enhance the response of both DHT and 2-OH-E2. The dose-response of DHT was biphasic in the presence and absence of FSH, such that progesterone production in the presence of 8 micrograms/ml DHT was similar to basal progesterone production. Concurrent treatment with saturating concentrations of 2-OH-E2 and DHT resulted in fully additive increases in progesterone production. Testosterone mimicked the effect of DHT. In comparison, concurrent treatment of saturating concentrations of 2-MeO-E2 and DHT or 2-MeO-E2 and 2-OH-E2 resulted in progesterone production that was only partially additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 Apr
PMID:Comparative effects of androgens and catecholestrogens on progesterone production by porcine granulosa cells. 283 47

Further studies were carried out on purified mouse Leydig cells to determine why they lose their hormone responsiveness after several days in monolayer culture. The effects of cholera-toxin on cyclic AMP and testosterone production were examined. It was found that cyclic AMP production could still be maximally stimulated by cholera-toxin after 4 days in culture when response to luteinizing hormone (LH) has declined. Testosterone production was, however, not maintained. Because this decline in testosterone production may have been due to the lack of a suitable substrate after several days in culture, cells were cultured initially in the presence of exogenous pregnenolone and low-density lipoproteins (LDL). Both substances were found to enhance basal and LH-stimulated testosterone production and to extend responsiveness of the cells until at least day 4, but by day 7 response was lost. Cells were then cultured in the presence of rat and human LDL and HDL and in both cases LDL was found to enhance consistently testosterone production, but HDL was much less effective. Scanning and transmission electron micrographs showed that changes in cell shape occurred during culture, but indicated that the cells were not depleted of lipid droplets by the end of culture or after LH stimulation. It is concluded that the eventual decline in testosterone synthesis is not due to lack of substrate, although the addition of exogenous substrate does extend the period of responsiveness. Nor is it due to a decrease in adenylate cyclase activity. At least part of the lesion is caused by a decrease in the enzymes required for the conversion of pregnenolone to testosterone.
Mol Cell Endocrinol 1985 Mar
PMID:The functional activity of adult mouse Leydig cells in monolayer culture: effect of lipoproteins, pregnenolone and cholera-toxin. 298 65

Inhibin production by cultured granulosa cells from immature diethylstilbestrol (DES)-primed rats was studied in relation to estradiol and progesterone production. The inhibin content in culture media was assayed with a specific radioimmunoassay (RIA) using an antibody to porcine 32 kDa inhibin that recognizes rat inhibin as well. Inhibin production was about 10 ng/ml/2 X 10(4) cells/72 h at the basal levels and was maximally stimulated with 25 ng/ml of follicle stimulating hormone (FSH) to 45 ng/ml which was 4.5 times the basal levels, with an ED50 value of 2.0 ng/ml. A cyclic AMP analog (dibutyryl cyclic AMP) or reagents that promote cAMP production were also effective in inhibin production, indicating that FSH stimulates inhibin production through a cAMP-dependent pathway. Luteinizing hormone (LH) was not effective in producing inhibin from freshly prepared granulosa cells, whereas granulosa cells pre-incubated with FSH for 48 h because responsive to LH regarding inhibin production. Testosterone sensitized the granulosa cells to the FSH stimulation, whereas hydrocortisone (4 ng/ml) decreased the sensitivity of granulosa cells by increasing the ED50 value for inhibin production by FSH about 10 times. A similar effect was observed regarding estradiol production, while progesterone production due to stimulation by FSH was enhanced by the hydrocortisone treatment. Insulin and platelet extract both stimulated inhibin production and enhanced the maximal response of inhibin production due to stimulation by FSH without altering, or even increasing the ED50 values. Epidermal growth factor (EGF), (D-Leu6)Des-Gly10-LHRH N-ethylamide (GnRH agonist) and 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent protein kinase C activator, inhibited both inhibin production and estradiol or progesterone production. Consequently, the regulation of inhibin production was similar to that of estradiol production, but markedly different from that of progesterone. However, inhibin and estradiol production were modulated differently by various growth factors and hormones. These phenomena might account for possible discrete changes in the plasma levels of inhibin and estradiol in vivo.
Mol Cell Endocrinol 1987 Dec
PMID:Regulation of inhibin production by rat granulosa cells. 312 10


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