Differentially regulated immediate early genes in the rat uterus.

Abstract

Estrogen stimulates cellular proliferation in the luminal epithelium, stroma, and smooth muscle of immature rat uterus. Progesterone administered concurrently with estrogen blocks the stimulatory effect of estrogen specifically in the epithelium, whereas progesterone administered alone stimulates proliferation in the endometrial stroma and myometrium. The present studies determined the effects of estrogen and progesterone on expression of the growth-associated, immediate early genes c-fos, c-jun, and jun-B in the luminal epithelium of the uterus. Hormonal effects were quantitated by Northern analysis of RNA extracted directly from the uterine luminal epithelium. Estrogen stimulated c-fos and jun-B expression, but repressed c-jun mRNA levels in the epithelium. In contrast, when whole organ RNA extracts were analyzed, estrogen increased mRNA levels for all three genes. Although progesterone administered alone showed no effect on mRNA levels in either epithelial or whole uterus extracts, it did attenuate the estrogen-induced increase in c-fos mRNA by 50% in whole uterus extracts and by 23% in epithelial extracts. The estrogen-induced increase in epithelial jun-B mRNA was not affected by progesterone pretreatment. Thus, in the immature rat uterus, no simple correlation exists between cellular proliferation and increased expression of the genes studied. However, progesterone completely blocked the repressive effect of estrogen on epithelial c-jun, suggesting a link between decreased c-jun expression and induction of cell proliferation in the uterine luminal epithelium. Estrogen repression of epithelial c-jun expression was hormone specific and sensitive to antiestrogen blockade. After estrogen treatment, epithelial c-jun mRNA decreased with a rate similar to its half-life, as determined in primary cultures of rat uterine cells. These results suggest that estrogen, acting through its receptor, directly represses transcription of c-jun in the uterine epithelium. Differences in hormonal regulation of immediate early genes between epithelial and nonepithelial uterine tissues probably results from tissue-specific transactivating factors that control the expression of these genes.