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Gonadotropin releasing hormone dependent regulation of gonadotropin subunit messenger rna levels in the rat


, : Gonadotropin releasing hormone dependent regulation of gonadotropin subunit messenger rna levels in the rat. Endocrinology 124(1): 272-278

The Nal-Glu GnRH antagonist (GnRHA) was given to castrate male and female rats 7 days after gonadectomy to assess the impact of selective GnRH inhibition on the steady state mRNA level of FSH.beta., LH.beta. and .alpha.-subunit and serum levels of FSH and LH. A low dose of GnRHA (125 .mu.g/kg .cntdot. day) given to female rats for 1, 3, or 7 days resulted in suppression of serum FSH and LH levels by 7 days to 50% and 40%, respectively, of ovariectomized control values. LH.beta. mRNA levels decreased in a time-dependent manner, so that by 7 days, LH.beta. mRNA levels were less than those in intact controls. There were significant but less dramatic declines in .alpha. and FSH.beta. mRNA levels. A higher dose of GnRHA (500 .mu.g/kg .cntdot. day) for 7 or 14 days administered to castrate male or female rats resulted in inhibition of serum LH and FSH to or below levels in intact controls. At this dose, all three gonadotropin subunit mRNA levels fell from castrate values toward or below those in intact controls. Thus, although low dose GnRHA administration supressed LH.beta. mRNA more than FSH.beta. mRNA levels, high dose GnRHA treatment resulted in equal suppression of all three gonadotropin subunits. No stimulatory effects on .alpha.-subunit mRNA levels were observed with either dose of GnRHA. We conclude that the pretranslational control of gonadotropin subunit biosynthesis is GnRH dependent. Adequate dose and length of administration of the potent Nal-Glu GnRHA results in suppression of both the serum gonadotropins FSH and LH and the mRNAs for FSH.beta., LH.beta. and .alpha.-subunit in female and male rats.

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