| First Author | Aupperlee MD | Year | 2009 |
| Journal | Endocrinology | Volume | 150 |
| Issue | 3 | Pages | 1485-94 |
| PubMed ID | 18988671 | Mgi Jnum | J:158091 |
| Mgi Id | MGI:4438004 | Doi | 10.1210/en.2008-1459 |
| Citation | Aupperlee MD, et al. (2009) Strain-specific differences in the mechanisms of progesterone regulation of murine mammary gland development. Endocrinology 150(3):1485-94 |
| abstractText | Progesterone (P) is required for normal mammary gland development, and is implicated in the etiology of mammary cancer in rodents and humans. We analyzed mammary gland developmental responses to P and estrogen (E) in two strains of mice (BALB/c and C57BL/6) that exhibit differences in ductal development at sexual maturity and alveologenesis during pregnancy. C57BL/6 mice exhibited reduced proliferative and morphological responses to P. Analysis of known mediators of sidebranching and alveologenesis revealed that reduced P-induced expression of P receptor isoform B and receptor activator of nuclear factor-kappaB ligand (RANKL), as well as altered expression and regulation of cyclin D1, CCAAT/enhancer binding protein beta, and the downstream effectors of RANKL, nuclear Id2 and p21, contribute significantly to the reduced P responsiveness of the C57BL/6 mammary gland. In contrast, E responsiveness was greater in C57BL/6 than in BALB/c glands. E may play a compensatory role in C57BL/6 alveologenesis through its effect on the induction and activation of signal transducer and activator of transcription 5a, a known regulator of RANKL. These observations suggest that in human populations with heterogeneous genetic backgrounds, individuals may respond differentially to the same hormone. Thus, genetic diversity may have a role in determining the effects of P in normal mammary development and tumorigenesis. |
