title: Follistatin suppresses steroid-enhanced follicle-stimulating hormone release in vitro in rats.
abstract: Previous in vitro and in vivo studies from our laboratory showed that progesterone (P(4)), corticosterone (B), and testosterone (T) increase intracellular content and release of FSH in the anterior pituitary. Activin (Act) and inhibin (Inh) are structurally related proteins with antagonistic actions, as Act stimulates and Inh inhibits FSH secretion from the anterior pituitary. Together with follistatin (FS), a protein that bioneutralizes Act, they form an autocrine-paracrine loop in the anterior pituitary that tightly regulates FSH secretion. The objective of the present study was to test the hypothesis that P(4), B, and T modulate this autocrine-paracrine loop to favor increased FSH secretion. If Act were to mediate steroid-induced FSH release, FS would be expected to block these effects. To test this interaction, cell cultures were prepared from anterior pituitaries of male and female rats, and treated with Act, B, P(4), or T in the absence or presence of FS. Act, B, P(4), and T increased FSH release; FS suppressed both basal and Act- and steroid-stimulated FSH release to approximately 50% below basal levels. Cell cultures from anterior pituitary of female rats were used to compare the interaction of incremental concentrations of FS on dose-related Act- and P(4)-stimulated FSH release. With increasing concentrations of Act, the FS-induced suppression of FSH release was attenuated and eventually abolished; in contrast, maximally stimulatory concentrations of P(4) did not fully overcome the FS-induced suppression of FSH release. The effects of P(4), B, and Act in the presence and absence of estradiol on steady-state mRNA levels of FSHbeta, Actbeta(B), and FS were determined in primary pituitary cell cultures from metestrous female rats by reverse transcription-polymerase chain reaction. Whereas Act, P(4), B increased FSHbeta mRNA levels, only Act raised the level of FS mRNA, and neither steroid increased Actbeta(B) mRNA. The results support the hypothesis that endogenous Act is a common mediator of the action of P(4), B, and T in the rat primary anterior pituitary cell culture. We conclude that the stimulation of FSH release and intracellular content in the gonadotroph by P(4), B, and T is mediated, in part, by Act and involves modulation of a tightly regulated Act/FS autocrine-paracrine loop.
authors.affiliation: Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Bohnsack
authors.forename: M
authors.initials: M
authors.lastname: Szabo
authors.forename: S M
authors.initials: SM
authors.lastname: Kilen
authors.forename: D H
authors.initials: DH
authors.lastname: Tam
authors.forename: N B
authors.initials: NB
authors.lastname: Schwartz
mesh_terms: D028341:Activins; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D007265:Inhibins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D012333:RNA, Messenger; D013256:Steroids; D028341:Activins; D013739:Testosterone; D011374:Progesterone; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D003345:Corticosterone