Gonadal Regulation of Gonadotropin Subunit Gene Expression: Evidence for Regulation of Follicle-Stimulating Hormone-β Messenger Ribonucleic Acid by Nonsteroidal Hormones in Female Rats*

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Abstract
Gonadectomy results in a rise in gonadotropin secretion and subunit gene expression, although the relative contributions of declining gonadal hormones or increasing hypothalamic GnRH secretion are uncertain. To further delineate the roles of the hypothalamus and gonads in regulation of gonadotropin gene expression, male and female rats were castrated and gonadotropin subunit messenger RNA (mRNA) concentrations measured 2,7,14, or 21 days (d) later. In males, FSH.beta. mRNA was maximal (2-fold increase) by 7 d while peak levels of .alpha. (3-fold) and LH.beta. (3-fold) were seen by 14 d. Testosterone (T) replacement restored all three subunit mRNA concentrations to intact values. In females, FSH.beta. mRNA also reached plateau levels (8-fold increase) earlier than .alpha. (3-fold) or LH.beta. (11-fold). When female rats ovariectomized 7 days earlier were given estradiol (E2) and progesterone (P) implants for up to 14 d, suppression of .alpha. and LH.beta. to intact levels was observed. However, FSH.beta. mRNA concentrations only decreased to 67% of castrate values, and remained 2- to 3-fold higher than levels in intact female rats. Female rats were also given E2 replacement at the time of ovariectomy. LH.beta. mRNA was maintained at intact levels for 14 days while .alpha. and FSH.beta. showed partial castration responses (2-fold and 3-fold, respectively). Finally, to determine whether E2 and P regulate gonadotropin subunit expression directly or by reducing GnRH secretion, female rats were ovariectomized and immediately replaced with E2, P, or E2 + P in the presence or absence of a GnRH antagonist (A) for 2 d. .alpha.mRNA was increased (2-fold) by E2 but not by E2 + A suggesting that E2 requires the presence of GnRH to increase .alpha.mRNA. P alone was ineffective, but both E2 and A prevented the LH.beta. mRNA response to ovariectomy. The effects of E2 and A were not additive, suggesting that E suppresses LH.beta. mRNA by inhibiting the increase in GnRH secretion. In contrast, the FSH.beta. mRNA response to ovariectomy was only partially suppressed by E2, E2 + P, or E2 + P + A. These data indicate that in castrate males, replacement of T suppresses all three subunit mRNAs to intact levels. However, replacement of E2 to ovariectomized females did not prevent the increase in .alpha. and FSH.beta. mRNAs. In female rats, LH.beta. mRNA is predominately regulated by GnRH. .alpha.mRNA expression is also mainly regulated by GnRH, and E2 appears to augment GnRH action on .alpha.mRNA expression. FSH.beta. gene expression is partially regulated by E2 and by GnRH, but ovariectomy also results in the loss of an additional gonadal inhibitory substance(s), possibly inhibin(s).

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