Progesterone inhibits the estrogen-induced expression of c-fos messenger ribonucleic acid in the uterus.

Estradiol produces a large increase in the uterine level of c-fos mRNA, which is maximum in 3 h. The administration of progesterone antagonizes this estrogen-induced increase in protooncogene transcript levels in both the rat and mouse. The inhibitory effect of progesterone is observed within 1 h after hormone treatment and persists for 9-18 h. In the rat, this effect can be observed at a dose of 0.25 mg progesterone and is maximum at a dose of 2.5 mg. A similar inhibition of fos mRNA levels after estrogen administration is produced by the glucocorticoid dexamethasone, but not by androgens or mineralocorticoids. Progesterone does not block the induction of c-jun or c-myc mRNA by estradiol. Uterine levels of c-fos mRNA observed after treatment with the phorbol ester phorbol 12-myristate 13-acetate are not decreased by a 3-h pretreatment with progesterone. Under the conditions of our experiments, progesterone does not decrease occupied levels of nuclear estrogen receptors in the uterus after estradiol administration. These findings are consistent with a mechanism in which progesterone inhibits transcriptional activation by the estrogen receptor at the level of the c-fos gene.