Are Mammalian Regulatory Systems Simple ?

Abstract

OHNO¹ suggests that the molecular biology of development of mammals is simpler than usually supposed. Certainly, the Tfm genetic variant should prove fruitful in investigating the mechanism of action of testosterone. Even accepting the validity of the proposed mode of action, however, the identification of one part of this regulatory system does not answer questions which may legitimately be asked about the molecular biology of sexual differentiation. It is not claimed that it tells us anything about the mechanism which induces the gonad to differentiate as a testis secreting testosterone in male animals but not in females; but neither does it give us any information as to how particular cells in both male and female animals come to possess the molecule (the Tfm protein¹) which enables them to respond to testosterone, whereas other cells do not. Again, among those cells which do produce the Tfm protein, there must be some prior regulation whereby the recognition of base sequences coding (in Ohno's example) for alcohol dehydrogenase and β-glucuronidase by the protein–testosterone complex (whether or not this involves Ohno's purely hypothetical homologous base sequences) occurs in kidney proximal tubule cells, but not in other target cells of testosterone where these enzymes are not induced. Yet these are the components of the regulatory system crucially responsible for differentiation between sexes and between tissues; whatever its mode of action may be, testosterone can only act as part of a switching mechanism in development by virtue of such components. In the context of classical embryology, Waddington has made a similar distinction between evocation and individuation².