期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 17, 页码 9744-9749出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1732707100
关键词
-
资金
- NICHD NIH HHS [HD 32007, R01 HD032007] Funding Source: Medline
Progesterone (P) regulates female reproduction via two nuclear receptors, PR-A and PR-B. Although both receptors display overlapping and distinct transcription regulatory properties, their individual physiological roles are unclear. To address the physiological role of PR-A, we generated a mouse model in which expression of PR-B was specifically ablated (PRBKO-/-) We show that selective activation of PR-A in PRBKO-/- mice is sufficient to elicit normal ovarian and uterine responses to P but re suits in reduced mammary gland morphogenesis. In the absence of PR-B, pregnancy-associated ductal sidebranching and lobuloalveolar development are markedly reduced due to decreased ductal and alveolar epithelial cell proliferation and decreased survival of alveolar epithelium. in an effort to elucidate the molecular genetic signaling pathways that are differentially regulated by PRs in the mammary gland, we have identified receptor (a) under bar ctivator of (n) under bar uclear (f) under bar actor kappaB (l) under bar igand (RANKL) as a paracrine mediator of P-dependent alveologenesis. Further, we demonstrate that the defects in PRBKO-/- mice are associated with an inability of PR-A to activate the RANKL signaling pathway in response to P. Our data indicate that functional interaction between PR-A and PR-13 is not required for reproductive activity and that selective modulation of PR-A activity by progestin agonists may have a protective effect against both uterine and mammary gland hyperplasias.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据