PMID- 24693965 OWN - NLM STAT- MEDLINE DCOM- 20140630 LR - 20211021 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 155 IP - 6 DP - 2014 Jun TI - Epidermal growth factor receptor (EGFR) signaling is a key mediator of hormone-induced leukocyte infiltration in the pubertal female mammary gland. PG - 2301-13 LID - 10.1210/en.2013-1933 [doi] AB - It is well documented that macrophages and eosinophils play important roles in normal murine pubertal mammary gland development. Although it is accepted that estrogen (E) and progesterone (P) are key players in mammary gland development, the roles these hormones might play in regulating the actions of leukocytes in that process is an understudied area. We show here that P and E, respectively, induce unique, but overlapping, sets of proinflammatory and angiogenic cytokines and chemokines, in the pubertal female BALB/c mammary gland, as well as induce infiltration of macrophages and eosinophils to the mammary periepithelium. This extends earlier studies showing P induction of proinflammatory products in pubertal and adult mammary epithelial organoids and P-induced in vivo infiltration of leukocytes to the adult mammary periepithelium. Importantly, epidermal growth factor receptor-signaling, which is likely mediated by amphiregulin (Areg), a downstream mediator of E and P, is both necessary and sufficient for both E- and P-induced recruitment of macrophages and eosinophils to the pubertal mammary periepithelium. We further show that receptor activator of nuclear factor kappaB ligand (RANKL), although not sufficient of itself to cause macrophage and eosinophil recruitment, contributes to an optimal response to P. The potency of Areg is highlighted by the fact that it is sufficient to induce macrophage and eosinophil recruitment at levels equivalent to that induced by either E or P. Our finding of a dominant role for Areg in hormonally induced leukocyte recruitment to the pubertal mammary gland parallels its dominance in regulating ductal outgrowth and its role in P-induced proliferation in the pubertal gland. FAU - Aupperlee, Mark D AU - Aupperlee MD AD - Breast Cancer and the Environment Research Program, Departments of Physiology (M.D.A., Y.Z., Y.S.T., J.R.L., J.B., S.Z.H.) and Microbiology and Molecular Genetics (R.C.S.), Michigan State University, East Lansing, Michigan 48824. FAU - Zhao, Yong AU - Zhao Y FAU - Tan, Ying Siow AU - Tan YS FAU - Leipprandt, Jeffrey R AU - Leipprandt JR FAU - Bennett, Jessica AU - Bennett J FAU - Haslam, Sandra Z AU - Haslam SZ FAU - Schwartz, Richard C AU - Schwartz RC LA - eng GR - U01 ES012800/ES/NIEHS NIH HHS/United States GR - U01 ES019434/ES/NIEHS NIH HHS/United States GR - 1U01ES12800/ES/NIEHS NIH HHS/United States GR - 1U01ESO19434/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140402 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Estrogens) RN - 0 (Isoenzymes) RN - 4G7DS2Q64Y (Progesterone) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.1.3.2 (Acid Phosphatase) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) SB - IM MH - Acid Phosphatase/pharmacology MH - Animals MH - ErbB Receptors/genetics/*metabolism MH - Estrogens/*pharmacology MH - Female MH - Fluorescent Antibody Technique MH - Isoenzymes/pharmacology MH - Leukocytes/*cytology MH - Mammary Glands, Animal/*drug effects/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Progesterone/*pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/drug effects MH - Tartrate-Resistant Acid Phosphatase PMC - PMC4020926 EDAT- 2014/04/04 06:00 MHDA- 2014/07/01 06:00 PMCR- 2015/06/01 CRDT- 2014/04/04 06:00 PHST- 2014/04/04 06:00 [entrez] PHST- 2014/04/04 06:00 [pubmed] PHST- 2014/07/01 06:00 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - EN-13-1933 [pii] AID - 10.1210/en.2013-1933 [doi] PST - ppublish SO - Endocrinology. 2014 Jun;155(6):2301-13. doi: 10.1210/en.2013-1933. Epub 2014 Apr 2.