title: Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts.
abstract: Estrogen and androgen are both critical for the maintenance of bone, but the target cells, mechanisms, and responses could be sex-specific. To compare sex-specific actions of estrogen and androgen on osteoclasts, human peripheral blood mononuclear precursor cells from adult Caucasian males (n = 3) and females (n = 3) were differentiated into osteoclasts and then treated for 24 h with 17β-estradiol (10 nM) or testosterone (10 nM). Gene expression was studied with a custom designed qPCR-based array containing 94 target genes related to bone and hormone action. In untreated osteoclasts, 4 genes showed significant gender differences. 17β-estradiol significantly affected 12 genes in osteoclasts from females and 6 genes in osteoclasts from males. Fifteen of the 18 17β-estradiol-responsive genes were different in the cells from the two sexes; 2 genes affected by 17β-estradiol in both sexes were regulated oppositely in the two sexes. Testosterone significantly affected 6 genes in osteoclasts from females and 2 genes in osteoclasts from males; all except one were different in the two sexes. 17β-estradiol and testosterone largely affected different genes, suggesting that conversion of testosterone to 17β-estradiol had a limited role in the responses. The findings indicate that although osteoclasts from both sexes respond to 17β-estradiol and testosterone, the effects of both 17β-estradiol and testosterone differ in the two sexes, highlighting the importance of considering gender in the design of therapy.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Paula H
authors.initials: PH
authors.lastname: Stern
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D013739:Testosterone; D004958:Estradiol