Androgens have Forgotten and Emerging Roles Outside of their Reproductive Functions, with Implications for Diseases and Disorders

Cellular and physiological responses to the androgens are mediated by the Androgen Receptor (AR) - a member of the steroid nuclear receptor superfamily. The AR is a ligand-dependent transcription factor that modulates the expression of androgen target genes. The AR and androgens are mainly thought of as being ‘male' hormones involved in the regulation of development of male reproductive tissues, anabolic effects and the development of male secondary sexual characteristics at puberty. However, recent development of mouse reporter models for androgen activity has confirmed that androgens not only have a wide variety of target tissues in the body but also have a variety of targets in both sexes. In males the testes secrete testosterone from metabolic adrenal sourced androgens, and are relatively high. In the female the ovaries and some peripheral tissues secrete androgens at a low level but may fluctuate with the estrous cycle. The androgen receptor is found to be expressed in many different tissues where its functions are relatively unknown. Given the fact that many domestic and agricultural animals are surgically gonadectomised they appear to be relatively healthy. However, the effects of androgens on non-reproductive organs are subtle and long lasting and may be hidden due to their complexity. Often the effects of androgen loss can only be seen in those undergoing hormone ablations e.g. for cancer therapies, or in the elderly where steroid hormone levels fall. This review reprises, re-evaluates and reminds us of the varied targets of androgens in the body, and how both sexes may be predisposed to certain diseases as a result.