title: Association of increased estrogen receptor beta2 expression with parity-induced alterations in the rat mammary gland.
abstract: In this study, we investigated the cellular and molecular events involved in parity-related alterations in mammary gland (MG) proliferation and differentiation. Rat MGs were removed on day 9 of either first (nulliparous), second (primiparous) or third (multiparous) pregnancy. Expression of steroid hormone receptors along with cellular biomarkers of proliferation and differentiation were quantified in all MG tissue compartments by immunohistochemistry. Wnt-4 (a Wingless-like morphogenic gene involved in MG development), ERbeta and ERbeta2 mRNA were evaluated by RT-PCR analysis. Serum levels of mammotrophic hormones were measured. In comparison to nulliparous and primiparous rats, multiparous animals exhibited decreased luminal cell proliferation and PR levels, whereas alpha-lactalbumin, ERalpha, ERbeta and ERbeta2 expression were increased. In myoepithelial cells, while parity induced a decrease in proliferative activity, subsequent pregnancies and lactations lead to an increased state of differentiation. Our results showed that at least two periods of pregnancy and lactation were necessary to modify the studied parameters. The lower proliferative activity and higher differentiation state of the multiparous MG are associated with both a decreased PR expression and increased ERalpha and ERbeta expression. Since ERbeta and/or ERbeta2 isoform expression was related to parity history, results suggest that the decreased proliferative activity and PR expression observed in the MG of multiparous animals may be associated with overexpression of ERbeta and/or the ERbeta2 isoform, thereby antagonizing the proliferative effects associated with ERalpha.
authors.affiliation: Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, C.C. 242, (3000) Santa Fe, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Kass
authors.forename: Milena
authors.initials: M
authors.lastname: Durando
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Ramos
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Varayoud
authors.forename: Charles E
authors.initials: CE
authors.lastname: Powell
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-de-Toro
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007768:Lactalbumin / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000378:metabolism*; D010298:Parity; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011270:Pregnancy, Animal; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051153:Wnt Proteins; D060528:Wnt4 Protein
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D012313:RNA; D007768:Lactalbumin