In some cell types testosterone interacts directly with androgen receptors while in others testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. Examples are derivatives of the Wolffian duct for the former, and derivatives of the urogenital sinus, the urogenital tubercle, and hair follicles for the latter.
The first known mechanism of action for androgen receptors was direct regulation of gene transcription. After androgen binds to an androgen receptor, restructuring with dimerization follows and the activated receptor complex enters the nucleus and binds to DNA. Androgen receptors interact with other proteins in the nucleus so as to cause alterations in gene transcription. Often the change in transcription is an activation resulting in formation of more messenger RNA that interacts with ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is insulin-like growth factor I (IGF-1). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
More recently, androgen recptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA[3]. Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
