Regulation of pituitary follistatin and inhibin/activin subunit messenger ribonucleic acids (mRNAs) in male and female rats: Evidence for inhibin regulation of follistatin mRNA in females

The regulation of FSH beta messenger RNA (mRNA) expression is complex and involves signals from the hypothalamus and gonads. Additionally, the local (pituitary) production of activin and follistatin appears to serve as an important modulator of endocrine signals for FSH beta regulation. The purpose of these studies was to identify factors controlling pituitary activin/inhibin subunit and follistatin mRNA production in male and female rats. Both males and females expressed the follistatin, inhibin alpha, and beta B mRNAs, whereas the beta A mRNA was not detected. In males, levels of FSH beta and follistatin were higher than those in females. After gonadectomy, levels of FSH beta and follistatin increased in both sexes, whereas beta B rose only in females. In males, blockade of GnRH action from the time of castration prevented the increase in FSH beta and follistatin, suggesting that GnRH is the primary stimulus for these gene products. In females, treatment with a GnRH antagonist only partially prevented the rise in FSH beta, follistatin, and PB expression, suggesting that other factors were also important. 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, suggesting that gonadal steroids may also act via local factors to regulate FSH beta. In summary, these studies provide evidence that GnRH, gonadal steroids, and gonadal peptides probably regulate FSH beta expression at least in part via the intrapituitary activin/follistatin system.