title: Prolactin regulates mammary epithelial cell proliferation via autocrine/paracrine mechanism.
abstract: Prolactin (PRL) is essential for a number of developmental events in the mammary gland. Work with PRL and PRL receptor knockout mice has shown that PRL indirectly regulates ductal side branching during puberty and directly controls lobuloalveolar development and lactogenesis during pregnancy. Anterior pituitary or placental PRL is thought to be responsible for these functions via an endocrine mechanism; however, PRL is also produced in a number of extrapituitary sites including the mammary gland. The physiologic relevance of mammary PRL remains unknown. In this study we utilized mammary recombination in Rag1(-/-) hosts, to determine whether mammary PRL plays a role in the regulation of mammary gland development. Mammary glands formed with the PRL gene deleted from either the epithelium, stroma, or both displayed normal development, on the basis of whole mount and hematoxylin and eosin histology, during puberty and lactation. At the end of pregnancy, a 2.8-fold decrease in bromodeoxyuridine incorporation was observed in the epithelial cells of mammary glands formed using PRL knockout epithelium compared with those formed using wildtype epithelium. No balancing alteration in the rates of apoptosis was detected. Thus, mammary-derived PRL influences mammary epithelial cell proliferation via an autocrine/paracrine mechanism, establishing a physiologic function for mammary PRL during mammopoiesis.
authors.affiliation: Cancer Research Program, The Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia. m.naylor@garvan.org.au
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Naylor
authors.forename: Jason A
authors.initials: JA
authors.lastname: Lockefeer
authors.forename: Nelson D
authors.initials: ND
authors.lastname: Horseman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019899:Paracrine Communication / Q000502:physiology; D011388:Prolactin / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein; D011388:Prolactin