Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone Receptor-B Isoform

• DOI: 10.1126/science.289.5485.1751
• Publication Date: 2002-07-27T09:35:26Z
• Authors: Biserka Mulac-Jer...; Robert A. Mullinax; Francesco J. DeMayo; John P. Lydon; Orla M. Conneely
• Keywords: Male; Mice, Knockout; Ovulation; 0301 basic medicine; Estradiol; Ovariectomy; Reproduction; Uterus; Epithelial Cells; Epithelium; Mice; 03 medical and health sciences; Mammary Glands, Animal; progesterone receptor-A ; and progesterone receptor-B ; knockout; Gene Expression Regulation; Animals; Protein Isoforms; Female; Embryo Implantation; Receptors, Progesterone; Cell Division; Crosses, Genetic; Progesterone

Progesterone regulates reproductive function through two intracellular receptors, progesterone receptor–A (PR-A) and progesterone receptor–B (PR-B), that arise from a single gene and function as transcriptional regulators of progesterone-responsive genes. Although in vitro studies show that PR isoforms can display different transcriptional regulatory activities, their physiological significance 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.