Gonadotropin-Releasing Hormone Desensitization Preferentially Inhibits Expression of the Luteinizing Hormone β-Subunit Genein Vivo

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Abstract
In this study we investigated changes in steady state cytoplasmic mRNA levels for LH subunits in pituitaries of male rats desensitized by continuous infusion of GnRH in vivo. Seven days of GnRH infusion (340 .mu.g/day) reduced (P < 0.01) LH.beta. mRNA levels in intact adult male rats and prevented the LH.beta. mRNA rise observed after castration. In contrast, common .alpha. mRNA doubled (P < 0.05) in intact rats, and the elevated .alpha. mRNA after 7 days castration was unchanged. Serum and pituitary LH levels were suppressed below values of intact controls. Fourteen days of GnRH infusion (290 .mu.g/day) further reduced LH.beta. mRNA levels in both intact and castrated male rat pituitaries. .alpha.mRNA levels in intact rat pituitaries were unchanged by 14 days of GnRH infusion, while in castrated rats there was a 23% (P < 0.05) decrease, though values were still twice those of intact controls. As at 7 days, serum and pituitary LH were suppressed. Infusion of a superagonist analog (Buserelin) at a dose of 14 .mu.g/day for 28 days reduced LH.beta. mRNA to 15% of intact control values in both castrated and intact rats. Common .alpha.mRNA was significantly (P < 0.05) increased in intact rats and reduced by 13% (P < 0.05) in castrates by superagonist infusion. These results were similar to those produced by 20- to 30-fold higher doses of native GnRH. GnRH and agonist analog effects were specific since no changes were observed in other mRNA species (GH, PRL, actin). These results indicate that in GnRH-desensitized gonadotropes LH.alpha. gene expression is inhibited, and this may largely explain the reduced LH biosynthesis. However, there is a differential effect of continuous GnRH or agonist analog treatment on LH subunit gene expression, with a time-dependent stimulation of common .alpha. gene expression in intact rats. This may be caused by a stimulatory interaction between GnRH and progestagens at the level of the gonadotrope. Thus, common .alpha. gene expression is less tightly coupled than that of LH.beta. to GnRH action.

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