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 FSHβ 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 FSHβ 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 α, and βB mRNAs, whereas the βA mRNA was not detected. In males, levels of FSHβ and follistatin were higher than those in females. After gonadectomy, levels of FSHβ and follistatin increased in both sexes, whereas βB rose only in females. In males, blockade of GnRH action from the time of castration prevented the increase in FSHβ 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 FSHβ, follistatin, and βB expression, suggesting that other factors were also important. Passive immunoneutralization of circulating inhibin increased FSHβ and follistatin (but not βB), providing evidence that inhibin is a physiological regulator of follistatin. Replacement of estradiol at the time of ovariectomy prevented the increase in βB mRNA, suggesting that gonadal steroids may also act via local factors to regulate FSHβ. In summary, these studies provide evidence that GnRH, gonadal steroids, and gonadal peptides probably regulate FSHβ expression at least in part via the intrapituitary activin/follistatin system.