Ovariectomy and inhibin immunoneutralization acutely increase follicle-stimulating hormone-beta messenger ribonucleic acid concentrations: evidence for a nontranscriptional mechanism

Abstract

After ovariectomy (ovx), FSH beta mRNA levels and serum FSH increase 2- to 3-fold within 12 h, and this persists in the presence of a GnRH antagonist. As a fall in plasma estradiol and progesterone appears to regulate FSH beta via increased GnRH secretion, it is thought that the acute (by 2 h) changes in FSH beta mRNA after ovx reflect falling levels of plasma inhibin. The current study addressed the following questions. 1) Does a reduction of circulating inhibin (via passive immunoneutralization or gonadectomy) increase FSH beta mRNA levels? 2) If so, are the acute increases in FSH beta mRNA associated with changes in the transcription rate? Adult male and female rats received 0.5 ml antiinhibin antiserum, iv, and were killed 2 or 12 h later. A second group of rats was gonadectomized; some received a GnRH antagonist and were killed at various intervals between 2 h and 7 days later. In adult males, no change in gonadotropin mRNA levels was observed after either addition of inhibin antiserum or removal of the testes. In contrast, in adult female rats, both ovx and inhibin antiserum increased FSH beta mRNA levels (2-fold) within 2 h, and a similar increase occurred in the presence of a GnRH antagonist. To determine if the increase in FSH beta resulted from increased mRNA synthesis, adult female rats were ovx, and half received a GnRH antagonist. Animals were killed 2 or 12 h later, and transcription rates were measured by nuclear run-off assay in pituitaries pooled from three rats. The transcription rate of the alpha-subunit, although not altered by ovx, was decreased in animals receiving the GnRH antagonist. Transcription of the LH beta gene was increased within 2 h after ovx, a change that was abolished by the GnRH antagonist. mRNA concentrations of either alpha or LH beta do not increase acutely after ovx, suggesting that GnRH regulates alpha and LH beta gene transcription and 12 h or more of mRNA synthesis are required to increase cytoplasmic concentrations. The FSH beta gene transcription rate was unchanged in both ovx and GnRH antagonist-treated animals, but serum FSH increased at 12 h. These data indicate that the rapid GnRH-independent increase in FSH beta mRNA levels seen immediately after ovx is not associated with altered mRNA synthesis and suggest that inhibin may also regulate FSH beta gene expression through nontranscriptional mechanisms.