[The regulation of gonadotropin receptor by the nonsteroidal intraovarian regulatory molecules during ovarian folliculogenesis].
The actions of FSH on ovarian follicular development and steroidogenesis are mediated through its binding to FSH receptors and required in the differentiation and maturation of ovarian follicles. Therefore it is clear that the ability of the gonadotropins to modulate ovarian function depends not only on the circulating levels of the gonadotropins, but also on the expression of appropriate receptor proteins by potential target cells in the ovary. We have observed a rapid and tentative down-regulation of FSH receptor mRNA after FSH treatment first time in granulosa cell culture. Using this culture cells, we investigated the mechanism of hormonal regulation of FSH receptor mRNA. The fact that both FSH and PMA show tentative down-regulation of FSH receptor mRNA suggests that these agents could be acting, at least in part, through a common mechanism, namely the activation of protein kinase C. Indeed, a role of the C kinase in cellular responses to hCG and TSH is consistent with findings that exposure to hCG or TSH stimulate the accumulation of inositol phosphates in nongonadal cells transfected with LH or TSH receptor. Activin, a stimulator or FSH secretion from the cultured pituitary cells, has been isolated from the mammalian follicular fluids and found to be a dimer of beta-subunits of inhibin. Activin has been shown to induce FSH receptor expression and FSH receptor mRNA on cultured rat granulosa cells. Since activin alone did not increase intracellular cAMP accumulation, to further clarify the role of activin and cAMP in the induction of FSH receptors, we examined the interactive effect of activin with cAMP on the induction of FSH receptors on cultured rat granulosa cells by 125I-FSH binding analysis. We have shown activin can up-regulate the expression of FSH receptor mRNA and protein by increasing both stability of mRNA and transcription rate. Using the cDNA clones of activin receptor type I and II, we have shown that both receptors are expressed in this cultured cells. This fact indicates that activin acts through autocrine/paracrine mechanism. On the other hands, follistatin can decrease the number of FSH binding sites elevated by addition of activin. Therefore, we examined the effects of endocrine manipulations (cAMP and PMA), FSH and activin, that are known to modulate granulosa cell function, on the follistatin productions. According to our data, these factors stimulate the production of follistatin mRNA in this cell culture, particularly the effect of activin on the follistatin mRNA indicates that the existence of negative regulation of activin effect by activin itself.(ABSTRACT TRUNCATED AT 400 WORDS)
Minegishi
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Department of Obstetrics and Gynecology, Gunma University School of Medicine.
D028341:Activins; D000818:Animals; D015536:Down-Regulation; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007265:Inhibins / Q000502:physiology*; D006080:Ovarian Follicle / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011967:Receptors, Gonadotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D038681:Follistatin; D006023:Glycoproteins; D012333:RNA, Messenger; D011967:Receptors, Gonadotropin; D028341:Activins; D007265:Inhibins