title: Strain-specific differences in the mechanisms of progesterone regulation of murine mammary gland development.
abstract: 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.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Aupperlee
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Drolet
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Durairaj
authors.forename: Weizhong
authors.initials: W
authors.lastname: Wang
authors.forename: Richard C
authors.initials: RC
authors.lastname: Schwartz
authors.forename: Sandra Z
authors.initials: SZ
authors.lastname: Haslam
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity
chemical_list: D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D004958:Estradiol