title: Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats.
abstract: It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlactation, whereas local administration of GnRH agonist (GnRHa) caused apoptosis of epithelial cells with ANXA5 augmentation in lactating rats. The latter treatment also decreased mammary weight, milk production, and casein accumulation. Mammary mast cells were strongly immunopositive for GnRH and the number increased in the mammary tissues after weaning. GnRHa was shown to be a chemoattractant for mast cells by mammary local administration of GnRHa and Boyden chamber assay. PRL suppressed the mammary expression of both ANXA5 and GnRH mRNA. It also decreased mast cell numbers in the gland after lactation. These results are the first to demonstrate that GnRH, synthesized locally in the mammary tissues, is required for mammary involution after lactation. GnRH is also suggested to introduce mast cells into the regressing mammary gland and would be in favor of tissue remodeling. The suppression of these processes by PRL is a novel physiological function of PRL.
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Duangjai
authors.initials: D
authors.lastname: Rieanrakwong
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Titaree
authors.initials: T
authors.lastname: Laoharatchatathanin
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Ryota
authors.initials: R
authors.lastname: Terashima
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yonezawa
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kurusu
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Laboratories of Veterinary Physiology (D.R., T.L., R.T., T.Y., S.K., M.K.) and Experimental Animal Science (Y.H.), School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Laboratory of Veterinary Clinical Pathology (T.Y.), Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; and Faculty of Veterinary Medicine (D.R., T.L.), Mahanakorn University of Technology, Bangkok 10530, Thailand.
authors.forename: Mitsumori
authors.initials: M
authors.lastname: Kawaminami
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007774:Lactation / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism; D008892:Milk / Q000378:metabolism; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017304:Annexin A5; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C083781:LHRH, Ala(6)-Gly(10)-ethylamide-; D011388:Prolactin; C062876:cetrorelix