Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Division / drug effects
-
Crosses, Genetic
-
Embryo Implantation*
-
Epithelial Cells / cytology
-
Epithelial Cells / drug effects
-
Epithelium / drug effects
-
Epithelium / metabolism
-
Estradiol / pharmacology
-
Female
-
Gene Expression Regulation
-
Male
-
Mammary Glands, Animal / cytology
-
Mammary Glands, Animal / drug effects
-
Mice
-
Mice, Knockout
-
Ovariectomy
-
Ovulation
-
Progesterone / pharmacology
-
Progesterone / physiology*
-
Protein Isoforms
-
Receptors, Progesterone / genetics
-
Receptors, Progesterone / physiology*
-
Reproduction*
-
Uterus / cytology
-
Uterus / drug effects
-
Uterus / metabolism
-
Uterus / physiology*
Substances
-
Protein Isoforms
-
Receptors, Progesterone
-
progesterone receptor A
-
progesterone receptor B
-
Progesterone
-
Estradiol