Regulation of low density lipoprotein receptor and cytochrome P-450scc mRNA levels in human granulosa cells

Abstract

hCG and 8-bromo-cAMP increase the levels of the mRNAs encoding the LDL receptor and cytochrome P-450scc in human granulosa cells. The increment in these mRNAs occurs rapidly after stimulation (within hours). Actin mRNA levels are not changed by hCG and 8-bromo-cAMP treatment. The tropic hormone effects on LDL receptor mRNA are observed even in the presence of 25-hydroxycholesterol and aminoglutethimide, which by themselves suppress LDL receptor mRNA. Actinomycin D blocks the hCG and 8-bromo-cAMP promoted augmentation of LDL receptor mRNA, suggesting that the tropic factors act to increase transcription of this gene. Treatment of cells with cycloheximide increases LDL receptor mRNA levels, and the stimulatory response to hCG and 8-bromo-cAMP is enhanced in the presence of cycloheximide. This indicates that tropic hormones act to increase LDL receptor mRNA levels without requiring synthesis of intermediary proteins and suggests that some short-lived protein may actually be reducing LDL receptors mRNA levels in these cells. We conclude that gonadotropins increase steroidogenesis in human granulosa cells, in part, by increasing expression of mRNAs encoding specific proteins involved in cholesterol metabolism.