Testosterone and the Male Skeleton: A Dual Mode of Action

Figure 1

Metabolism of sex steroids. (i) Testosterone (T), that is secreted by the testes, can directly act on its receptor, the androgen receptor (AR), present in bone cells. (ii) T can also be converted locally to dihydrotestosterone (DHT) by 5α-reductase. (iii) In addition, T can undergo aromatization to 17β-estradiol (E₂) by aromatase. E₂acts on one or both estrogen receptors (ERα or ERβ). (iv) The adrenals secrete C19 androgens including dehydroepiandrosterone (DHEA) that can also be converted to (v) estrone (E₁) and E₂by aromatase, 17β-hydroxysteroid dehydrogenase (17β-HSD), and 3β-HSD or to T by 17β-HSD and/or 3β-HSD. (vi) In men and women, T and E₂are predominantly bound to sex hormone binding globulin (SHBG), synthesized by the liver.