CELLULAR-PATTERN OF C-FOS INDUCTION BY ESTRADIOL IN THE IMMATURE RAT UTERUS

Previous biochemical studies have shown that c-fos mRNA expression is rapidly and dramatically induced by estrogen in the immature rat uteru s. In this work we have used in situ hybridization and immunocytochemi stry to analyze the cellular pattern of proto-oncogene induction follo wing administration of estradiol. The c-fos transcript and protein lev els were low in control animals. Three hours after hormone treatment, the luminal and glandular epithelium, stroma, and myometrium all showe d a clear increase in mRNA levels of the proto-oncogene as judged by i n situ hybridization; this increase was most pronounced in the epithel ial cells. Immunocytochemistry also demonstrated Fos expression in all cell layers with a higher fraction of cells staining in the epithelia l and stromal layers than in the myometrium. Estradiol thus increased expression of c-fos in all major cell types of the immature uterus, al though each tissue layer exhibited a specific pattern and degree of fo s transcript and protein expression. This proto-oncogene is thus a mar ker for estrogen action in all uterine cell types at this stage of dev elopment. Since estrogen stimulates proliferation in all cell layers o f the immature uterus, the cellular pattern of fos expression also cor relates with the proliferative response to the hormone.