Sex-Specific Effects of Estrogen and Androgen on Gene Expression in Human Monocyte-Derived Osteoclasts

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 17 beta-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. 17 beta-estradiol significantly affected 12 genes in osteoclasts from females and 6 genes in osteoclasts from males. Fifteen of the 18 17 beta-estradiol-responsive genes were different in the cells from the two sexes; 2 genes affected by 17 beta-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. 17 beta-estradiol and testosterone largely affected different genes, suggesting that conversion of testosterone to 17 beta-estradiol had a limited role in the responses. The findings indicate that although osteoclasts from both sexes respond to 17 beta-estradiol and testosterone, the effects of both 17 beta-estradiol and testosterone differ in the two sexes, highlighting the importance of considering gender in the design of therapy. J. Cell. Biochem. 112: 3714-3721, 2011. (C) 2011 Wiley Periodicals, Inc.