Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform.
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.
Mulac-Jericevic
B
B
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Mullinax
R A
RA
DeMayo
F J
FJ
Lydon
J P
JP
Conneely
O M
OM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003433:Crosses, Genetic; D010064:Embryo Implantation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D010060:Ovulation; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D020033:Protein Isoforms; D011980:Receptors, Progesterone / Q000235:genetics / Q000502:physiology*; D012098:Reproduction; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D020033:Protein Isoforms; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D004958:Estradiol