Gonadal regulation of pituitary hormone mRNA levels in male rats

Abstract

ABSTRACT The control of anterior pituitary hormone gene expression by testosterone in male rat pituitaries in vivo was investigated using dot-blot mRNA-cDNA hybridization assays. Common α subunit mRNA levels doubled by 2 days after orchidectomy and rose progressively to reach plateau levels three to four times intact control values by 2 weeks. LH-β mRNA increased significantly (≃50%) within 12h, and thereafter progressively to seven times intact control values by 3 weeks after orchidectomy. The changes in α mRNA were likely to have occurred in gonadotrophs and not thyrotrophs, since TSH-β mRNA levels were unaltered by orchidectomy. LH subunit mRNA changes were accompanied by an initial (1–4 days) decrease in pituitary LH content; thereafter, pituitary LH increased in parallel with and by a similar magnitude to the LH-β mRNA. Serum LH rises occurred before significant increases in LH subunit mRNA after orchidectomy. The lack of temporal correlation between mRNA levels and serum and pituitary LH in the early stages after removal of testosterone feedback contrasts with the good correlation when a new steady state was achieved after 3–4 weeks, and indicates differing kinetics for changes in these aspects of gonadotroph function. An inhibitory effect of testosterone on LH subunit gene expression was confirmed by prevention of the rise in α and LH-β mRNAs when treatment commenced immediately after castration. However, pituitary LH content and serum LH levels were reduced relative to control values, suggesting additional inhibitory actions of testosterone on translational and post-translational events in gonadotrophs. A stimulatory effect of testosterone on α mRNA levels was observed between 4 and 24 h after a single injection in rats castrated 2 weeks previously, no effect being seen on LH-β mRNA. The mechanism for this action remains to be elucidated. Gene specificity of testosterone action was confirmed by unaltered levels of mRNA for prolactin, GH, TSH-β subunit and actin under all experimental conditions. No changes in pituitary content of prolactin or GH were found. We conclude that regulation of LH subunit gene expression by testosterone is an important step in control of gonadotrophin synthesis and availability for release.