Chronic inhibitory effect of follicle-stimulating hormone (FSH)-suppressing protein (FSP) or follistatin on activin- and gonadotropin-releasing hormone-stimulated FSH synthesis and secretion in cultured rat anterior pituitary cells.
The effects of bovine FSH-suppressing protein (FSP) or follistatin on activin- and GnRH-stimulated FSH synthesis and secretion have been studied using cultured pituitary cells from adult male Sprague-Dawley rats. Exposure to FSP (0.001-10 nM) for 3 days dose-dependently suppressed basal FSH secretion (IC50 = 146 +/- 21 pM., mean +/- SE), cellular content (IC50 = 269 +/- 8 pM) and total FSH (IC50 = 181 +/- 25 pM), with no effect on LH. Activin (0.3 nM) increased FSH secretion 2.1-fold, cellular content 1.3-fold, and total FSH 1.9-fold during a 3-day incubation, but these increases were dose-dependently inhibited by concomitant treatment with 35-kDa bovine FSP (0.1-3 nM), with complete inhibition occurring at concentrations between 1 and 3 nM. The 31- and 39-kDa forms of bovine FSP also antagonized the actions of activin. GnRH (1 nM) increased FSH secretion 1.8-fold and total FSH 1.6-fold during a 3-day incubation, effects that were dose-dependently inhibited by concomitant treatment with 35-kDa bovine FSP. The highest tested concentration of FSP (3 nM) suppressed GnRH-stimulated FSH secretion and total FSH to 59 and 57%, respectively, of the levels found in untreated cultures. All three forms of bovine FSP produced a significant inhibition of FSH secretion and total FSH stimulated by GnRH. FSP also suppressed FSH secretion and total FSH in response to activators of protein kinase C including 100 nM phorbol 12-myristate 13-acetate (43 and 59%, respectively) and 100 nM mezerein (40 and 60%, respectively). Finally, treatment of cultured pituitary cells with 35-kDa FSP at 1 and 3 nM for 3 days resulted in 21 and 24% decreases in GnRH binding sites, respectively. It is concluded that (i) FSP inhibits not only the secretion but also the synthesis of FSH induced by activin and GnRH in long-term culture, and (ii) FSP may cause its inhibitory effects on GnRH by suppression of the protein kinase C system, and possibly by reduction of GnRH binding sites.
Wang
Q F
QF
Prince Henry's Institute of Medical Research, South Melbourne, Victoria, Australia.
Farnworth
P G
PG
Findlay
J K
JK
Burger
H G
HG
D028341:Activins; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis / Q000378:metabolism*; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D007265:Inhibins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004224:Diterpenes; D038681:Follistatin; D006023:Glycoproteins; D013729:Terpenes; D028341:Activins; D007987:Gonadotropin-Releasing Hormone; C011309:mezerein; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate