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.
Kirkland
J L
JL
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Murthy
L
L
Stancel
G M
GM
D000818:Animals; D016375:Antisense Elements (Genetics); D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D016375:Antisense Elements (Genetics); D015347:RNA Probes; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D012313:RNA; D013755:Tetradecanoylphorbol Acetate