Enigmas in the Molecular Biology of Androgen Action

It has been said that a valuable scientific hypothesis is not so much a cogent explanation of phenomena as a successful policy for research. For more than fifteen years it has become increasingly accepted that control of gene expression mechanisms is a salient feature of androgen action, and that somehow or other, androgens profoundly influence the transcription of specific genes in the nuclei of target cells (Mainwaring 1977; Williams-Ashman 1965; Williams-Ashman and Reddi 1972). Around the turn of this decade, specific androgen-receptor proteins were discovered in a number of responsive tissues. These receptors interact firmly with testosterone and even more tenaciously with 5α-dihydrotestosterone (DHT), a major metabolite of circulating testosterone in many but not all androgen-sensitive cells. The androgen-receptor complexes are readily translocated into cell nuclei and retained there in association with chromatin (Jensen et al. 1977; Liao, 1975; Liao and Fang 1969; Mainwaring, 1977; Williams-Ashman 1975; Williams- Ashman and Reddi 1971; Wilson and Gloyna 1970). However despite various claims that DHT-receptor complexes can directly stimulate RNA polymerase reactions in isolated nuclear preparations, the mechanisms by which these hormones affect RNA transcription and processing in the nucleus remain enigmatic.