Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts

J Cell Biochem. 2011 Dec;112(12):3714-21. doi: 10.1002/jcb.23297.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Estradiol / pharmacology*
  • Female
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Humans
  • Male
  • Monocytes / drug effects*
  • Osteoblasts / drug effects*
  • Sex Factors*
  • Testosterone / pharmacology*

Substances

  • Testosterone
  • Estradiol