Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone

Progesterone regulates reproductive function through two intracellular recep-tors, progesterone receptorÐA (PR-A) and progesterone receptorÐB (PR-B), that arise from a single gene and function as transcriptional regulators of proges-terone-responsive genes. Although in vitro studies show that PR isoforms can display different transcriptional regulatory activities, their physiological sig-niÞcance is unknown. By selective ablation of PR-A in mice, we show that the PR-B isoform modulates a subset of reproductive functions of progesterone by regulation of a subset of progesterone-responsive target genes. Thus, PR-A and PR-B are functionally distinct mediators of progesterone action in vivo and should provide suitable targets for generation of tissue-selective progestins. The steroid hormone progesterone (P) functions in establishment and maintenance of pregnan-cy. The physiological effects of P are mediated by interaction with specific intracellular proges-terone receptors (PRs) that are members of th