title: Prolactin decreases expression of Runx2, osteoprotegerin, and RANKL in primary osteoblasts derived from tibiae of adult female rats.
abstract: Hyperprolactinemia caused by physiological or pathological conditions, such as those occurring during lactation and prolactinoma, respectively, results in progressive osteopenia. The underlying mechanisms, however, are controversial. Prolactin (PRL) may directly attenuate the functions of osteoblasts, since these bone cells express PRL receptors. The present study therefore aimed to investigate the effects of PRL on the expression of genes related to the osteoblast functions by using quantitative real-time PCR technique. Herein, we used primary osteoblasts that were derived from the tibiae of adult rats and displayed characteristics of differentiated osteoblasts, including in vitro mineralization. Osteoblasts exposed for 48 h to 1000 ng/mL PRL, but not to 10 or 100 ng/mL PRL, showed decreases in the mRNA expression of Runx2, osteoprotegerin (OPG), and receptor activator of nuclear factor kappaBeta ligand (RANKL) by 60.49%, 72.74%, and 87.51%, respectively. Nevertheless, PRL did not change the RANKL/OPG ratio, since expression of OPG and RANKL were proportionally decreased. These concentrations of PRL had no effect on the mRNA expression of osteocalcin and osteopontin, nor on mineralization. High pathologic concentrations of PRL (1000 ng/mL) may downregulate expression of genes that are essential for osteoblast differentiation and functions. The present results explained the clinical findings of hyperprolactinemia-induced bone loss.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. naratt@narattsys.com
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
authors.forename: Jarinthorn
authors.initials: J
authors.lastname: Teerapornpuntakit
authors.forename: Methajit
authors.initials: M
authors.lastname: Methawasin
authors.forename: Kannikar
authors.initials: K
authors.lastname: Wongdee
authors.forename: Kanogwun
authors.initials: K
authors.lastname: Thongchote
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C493717:Runx2 protein, rat; C506897:Spp1 protein, rat; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D011388:Prolactin