Mulac-Jericevic B, Mullinax R A, DeMayo F J, Lydon J P, Conneely O M
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Science. 2000 Sep 8;289(5485):1751-4. doi: 10.1126/science.289.5485.1751.
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.
孕酮通过两种细胞内受体——孕酮受体-A（PR-A）和孕酮受体-B（PR-B）调节生殖功能，这两种受体由单个基因产生，作为孕酮反应基因的转录调节因子发挥作用。尽管体外研究表明PR异构体可表现出不同的转录调节活性，但其生理意义尚不清楚。通过在小鼠中选择性地敲除PR-A，我们发现PR-B异构体通过调节一部分孕酮反应靶基因来调节孕酮的一部分生殖功能。因此，PR-A和PR-B在体内是孕酮作用的功能不同的介质，应该为生成组织选择性孕激素提供合适的靶点。
