Sex‐specific gene responses to estrogen and androgen in human osteoclasts

Abstract

Estrogen and androgen are both critical for 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 (OC), mononuclear precursor cells from adult Caucasian males (n=3) and females (n=3) were differentiated into OC and then treated for 24 h with 10nM 17β‐estradiol (E2) or testosterone (T), or ethanol (control). Gene expression was studied with a custom designed qPCR array containing 94 target genes related to bone and hormone action. Genes changed > 2 fold with p<0.05 were considered significantly modified. In untreated OC, 4 genes showed significant gender differences. E2 significantly affected 12 genes in OC from females and 6 genes in OC from males. 15 of the 18 E2‐responsive genes differed in cells from the two sexes. 2 of the genes affected by E2 in both sexes were regulated oppositely in the two sexes. T significantly affected 6 genes in OC from females and 2 genes in OC from males; all except one gene were different in the two sexes. The findings indicate that 1) OC from both sexes are affected by both E2 and T; 2) within the genes examined, more were affected in OC from females than males; 3) effects of both E2 and T differ in the two sexes; 4) E2 and T largely affect different genes, suggesting that conversion of T to E2 has a limited role in the gene responses.Support: Northwestern Univ. Institute for Womens Health Research.