Disorders of androgen biosynthesis

Disorders of androgen biosynthesis are a relatively rare cause of sexual ambiguity in 46,XY genetic males, but genetic disorders characterized by excessive androgen synthesis are a common cause of virilization in 46,XX genetic females. Understanding of these disorders is relatively simple if one is familiar with the components of the various steroidogenic pathways. The biosynthesis of androgens requires the steroidogenic acute regulatory protein (StAR) and the steroidogenic enzymes P450scc, P450c17, 3betaHSDII, 17betaHSDIII, and 5alpha-reductase. Deficiencies have been described in all of these, leading to male pseudohermaphroditism. Other steroidogenic enzymes not involved in androgen biosynthesis, such as P450c21, P450c11beta, and P450aro, must also be considered, as mutations in these can result in overproduction of androgens, resulting in female pseudohermaphroditism.