Neonatal endocrinology of abnormal male sexual differentiation: molecular aspects

Normal male sexual differentiation is a complex mechanism, depending on genetic and hormonal control. The bipotent gonad arises at the genital ridge under the control of autosomal genes which are also involved in the formation of other organs. Progression towards testicular differentiation is mediated through both autosomal and gonosomal genes, leading to alignment of Sertoli cells and Leydig cells. Within the latter, androgen formation is induced by human chorionic gonadotrophin and luteinizing hormone. The influence of testosterone and dihydrotestosterone leads to differentiation of epidydimis, vasa deferentia, prostate and external genitalia. Androgens mediate their action through the androgen receptor, a nuclear transcription factor controlling the regulation of so far unknown target genes. Genetic variations within this pathway interrupt normal male development and will lead to malformation of external and/or internal genitalia.