Identification of androgen-regulated genes

Androgens are essential for skeletal growth and bone accrual during puberty and for bone maintenance post-puberty in males, determining both the strength and size of adult bone. Russell et al had earlier shown that global deletion of the androgen receptor (AR) in mice results in bones of reduced size and cortical thickness, with decreased trabecular bone volume compared with control males indicating that these important actions of androgens are via the AR in bone. However, the exact mechanism by which androgens exert these actions via the AR on bone remains unclear.

To investigate the mechanisms by which androgens exert their effects via the AR in mineralizing osteoblasts and osteocytes, they identified gene targets/pathways regulated by the AR using targeted gene expression and microarray approaches on bone isolated from mice in which the AR is specifically deleted in mineralizing osteoblasts and osteocytes (mOBL-ARKOs).

The osteoblast genes Col1a1 and Bglap and the osteoclast genes Ctsk and RANKL (Tnfs11) were upregulated in the bones of mOBL-ARKOs, consistent with the increased matrix synthesis, mineralization, and bone resorption observed previously in these mice. Interestingly, they identified genes involved in carbohydrate metabolism (adiponectin and Dpp4) and in growth and development (GH, Tgfb (Tgfb2), Wnt4) as potential targets of androgen action via the AR in mineralizing osteoblasts. Russell et al. (2012) Journal of Molecular Endocrinology 49 1-10.

Read the full article at DOI: 10.1530/JME-12-0014