title: Hypothyroidism decreases JAK/STAT signaling pathway in lactating rat mammary gland.
abstract: Thyroid pathologies have deleterious effects on lactation. Especially hypothyroidism (HypoT) induces premature mammary involution at the end of lactation and decreases milk production and quality in mid lactation. Milk synthesis is controlled by JAK2/STAT5 signaling pathway and prolactin (PRL), which activates the pathway. In this work we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on PRL signaling pathway on mammary glands from rats on lactation (L) days 2, 7 and 14. HypoT decreased prolactin receptor expression, and expression and activation of Stat5a/b protein. Expression of members of the SOCS-CIS family, inhibitors of the JAK-STAT pathway, decreased in L2 and L7, possibly as a compensatory response of the mammary cells to maintain PRL responsiveness. However, on L14, the level of these inhibitors was normal and the transcription of α-lactoalbumin (lalba), a target gene of the PRL pathway, decreased by half. HypoT altered the transcriptional capacity of the cell and decreased mRNA levels of Prlr and Stat5b on L14. Stat5b gene has functional thyroid hormone response elements in the regulatory regions, that bind thyroid hormone receptor β (TRβ) differentially and in a thyroid hormone dependent manner. The overall decrease in the PRL signaling pathway and consequently in target gene (lalba) mRNA transcription explain the profound negative impact of HypoT on mammary function through lactation.
authors.affiliation: Laboratorio de Reproducción y Lactancia, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, 5500 Mendoza, Argentina. Electronic address: farbocco@mendoza-conicet.gob.ar.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Campo Verde Arboccó
authors.affiliation: Laboratory of Hormones and Biology of Cancer, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), Argentina.
authors.forename: Fabio Andres
authors.initials: FA
authors.lastname: Persia
authors.affiliation: Laboratorio de Reproducción y Lactancia, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, 5500 Mendoza, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Hapon
authors.affiliation: Laboratorio de Reproducción y Lactancia, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, 5500 Mendoza, Argentina. Electronic address: gjahn@mendoza-conicet.gob.ar.
authors.forename: Graciela A
authors.initials: GA
authors.lastname: Jahn
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism*; D007774:Lactation / Q000378:metabolism*; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D011401:Promoter Regions, Genetic / Q000235:genetics; D011441:Propylthiouracil; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013972:Thyrotropin / Q000097:blood
chemical_list: D012333:RNA, Messenger; D050791:STAT Transcription Factors; D011441:Propylthiouracil; D011388:Prolactin; D013972:Thyrotropin; D053612:Janus Kinases
keywords: Hypothyroidism; JAK/STAT signaling; Lactation