Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform

摘要: Progesterone (P) regulates female reproduction via two nuclear receptors, PR-A and PR-B. Although both receptors display overlapping distinct transcription regulatory properties, their individual physiological roles are unclear. To address the role of PR-A, we generated a mouse model in which expression PR-B was specifically ablated (PRBKO–/–). We show that selective activation PRBKO–/– mice is sufficient to elicit normal ovarian uterine responses P but results reduced mammary gland morphogenesis. In absence PR-B, pregnancy-associated ductal sidebranching lobuloalveolar development markedly due decreased alveolar epithelial cell proliferation survival epithelium. an effort elucidate molecular genetic signaling pathways differentially regulated by PRs gland, have identified receptor activator factor κB ligand (RANKL) as paracrine mediator P-dependent alveologenesis. Further, demonstrate defects associated with inability activate RANKL pathway response P. Our data indicate functional interaction between not required for reproductive activity modulation progestin agonists may protective effect against hyperplasias.