Limitations of the Model of Androgen Action

Abstract

As discussed at length by King and Mainwaring (1974), models for the mechanism of action of all steroid hormones are remarkably similar and despite pro found differences in the nature of the biological responses, all are believed to be initiated by receptor protein-hormone interactions. All responses essentially fall into two distinct categories, switch (inaugural) processes or amplification (modulation) phenomena. In fundamental terms, switch processes may be equated with the qualitative changes promoted by steroid hormones whereas amplification processes embrace purely quantitative changes. Switch processes controlled by androgens are surprisingly few, but based primarily on the classical studies of JOST (1953; 1967; 1970) it is now accepted that the development of the male phenotype and the differentiation of the male urogenital tract, except for the regression of the Müllerian duct, is promoted by the secretion of testosterone from the foetal testis. This profound change during a critical phase of embryonic development is a prime example of a switch mechanism controlled by androgens. Nearly all the other processes regulated by androgens, especially in adult animals, may safely be described as amplification phenomena. Inspection of Figure 1 fails to show how receptor mechanisms alone can initiate switch as against amplification processes. Other components in the genetic apparatus must be implicated in establishing the mode of hormonal responses, but the nature of these subtle regulators is totally unknown.