GONADOTROPIN SUBUNIT MESSENGER-RNA CONCENTRATIONS AFTER BLOCKADE OF GONADOTROPIN-RELEASING-HORMONE ACTION - TESTOSTERONE SELECTIVELY INCREASES FOLLICLE-STIMULATING-HORMONE BETA-SUBUNIT MESSENGER-RNA BY POSTTRANSCRIPTIONAL MECHANISMS

Regulation of gonadotropin gene expression by sex steroids may occur via direct effects on the pituitary and/or indirect effects of steroids mediated through hypothalamic GnRH. We aimed to define the effects of testosterone (T) on alpha, LH-beta, and FSH-beta mRNA expression in the male rat after blockade of GnRH action on the gonadotrope. A water-soluble GnRH antagonist was administered iv to castrate male rats (increased endogenous GnRH secretion) and to castrate T-replaced rats in which gonadotropin subunit mRNAs had been increased by prior treatment with exogneous GnRH pulses. In castrate male rats, GnRH antagonist resulted in a fall in all three subunit mRNAs. Alpha and LH-beta declined at slower rates (half-disappearance after 50 and 65 h, respectively), and neither fell to values present in intact rats over 84 h. In contrast, FSH-beta mRNA declined more rapidly, with a half-disappearance after 20 h. In castrate T-replaced rats, alpha-mRNA declined at a rate similar to that in castrates (half-disappearance after 50 h). LH-beta declined more slowly, and the rate of FSH-beta decline was markedly prolonged in the presence of T (half-disappearance time increased from 20 to 50 h). These results suggest that T exerts direct effects on FSH-beta transcription or mRNA stability which are independent of GnRH action. To assess these possibilities, a long-acting GnRH antagonist (Detirelix) was administered to castrate male rats, which also received T or sham implants 4 days after castration. FSH-beta mRNA levels fell during the 4 days of Detirelix alone, but the addition of T on day 4 resulted in a 2-fold rise in FSH-beta mRNA, restoring FSH-beta mRNA to levels present in intact rats. Serum FSH closely paralleled FSH-beta mRNA concentrations. Alpha mRNA was reduced by 25% and the LH-beta mRNA concentrations were unchanged in the presence of T. The rate of alpha mRNA transcription was markedly reduced and that of LH-beta tended to fall in T-treated rats, but T had no significant effect on the FSH-beta transcription rate. Thus, the action of T to increase concentrations of cytosolic FSH-beta mRNA appears to be exerted at a posttrascriptional level, possibly via effects of T on FHS-beta mRNA stability. This may represent a mechanism by which T can effect differential regulation of gonadotropin subunit mRNA concentrations. (Molecular Endocrinology 4: 1943-1955, 1990)