REGULATION OF PITUITARY FOLLISTATIN AND INHIBIN ACTIVIN SUBUNIT MESSENGER RIBONUCLEIC-ACIDS (MESSENGER-RNAS) IN MALE AND FEMALE RATS - EVIDENCE FOR INHIBIN REGULATION OF FOLLISTATIN MESSENGER-RNA IN FEMALES/

The regulation of FSH beta messenger RNA (mRNA) expression is complex and involves signals from the hypothalamus and gonads. Additionally, t he local (pituitary) production of activin and follistatin appears to serve as an important modulator of endocrine signals for FSH beta regu lation. The purpose of these studies was to identify factors controlli ng pituitary activin/inhibin subunit and follistatin mRNA production i n male and female rats. Both males and females expressed the follistat in, inhibin alpha, and beta B mRNAs, whereas the beta A mRNA was not d etected. In males, levels of FSH beta and follistatin were higher than those in females. After gonadectomy, levels of FSH beta and follistat in increased in both sexes, whereas beta B rose only in females. In ma les, blockade of GnRH action from the time of castration prevented the increase in FSH beta and follistatin, suggesting that GnRH is the pri mary stimulus for these gene products. In females, treatment with a Gn RH antagonist only partially prevented the rise in FSH beta, follistat in, and PB expression, suggesting that other factors were also importa nt. Passive immunoneutralization of circulating inhibin increased FSH beta and follistatin (but not beta B), providing evidence that inhibin is a physiological regulator of follistatin. Replacement of estradiol at the time of ovariectomy prevented the increase in beta B mRNA, sug gesting that gonadal steroids may also act via local factors to regula te FSH beta. In summary, these studies provide evidence that GnRH, gon adal steroids, and gonadal peptides probably regulate FSH beta express ion at least in part via the intrapituitary activin/follistatin system .