GONADAL-STEROIDS EFFECT SIMILAR REGULATION OF GONADOTROPIN SUBUNIT MESSENGER-RNA EXPRESSION IN BOTH MALE AND FEMALE RATS

Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-beta mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 +/- 4 ng/l) in males or testosterone (plasma testosterone 3.5 +/- 0.3-mu-g/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dot-blot hybridization. In males, oestradiol reduced LH-beta and FSH-beta but not alpha-mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-beta remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced-alpha and LH-beta to levels found in intact animals. FSH-beta mRNA was partially reduced by antagonist alone in ovariectomized females but the addition of testosterone increased FSH-beta twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone increased FSH-beta twofold versus antagonist alone (as has been observed in males). These findings, together with earlier data, suggest that testosterone reduces gonadotrophin subunit mRNAs by inhibiting GnRH secretion and also acts directly on the gonadotroph to increase steady-state FSH-beta mRNA concentrations in both males and females.