1994 Volume 85 Issue 8 Pages 1189-1212
Male pseudohermaphroditism (MPH) is a complex variety of sexual differentiation disorders characterized by deficiency of masculinization of the internal and/or external genital organs in the presence of testicular development as the male gonad. This condition is caused by embryonic failure in the processes of male sexual development, which is a sequence of mechanisms originating from the genetic sex determination triggered by the SRY gene on the Y chromosome, followed by genital sex differentiation influenced by the fetal testis. Resulting phenotypical features of MPH vary from complete female to mostly normal but with some abmiguity in the maleness. Pubertal changes are also important factors related to etiology. Recent elucidation of detailed mechanisms of male differentiation and its derrangements has been achieved in the era of molecular genetics. Classical classification of MPH, mainly based on anatomical and endocrinological findings obviously needs to subject to a complete revision. The newest version of MPH classification is reviewed and discussed in relation to etiological backgrounds of each type of the disorder.
Main etiological factors are: failure of the SRY and its related genes involved in the testis determination; failure of anti-mülerian hormone (AMH) for normal involution of the female duct system; disordered production or function of androgen receptors essential for the fetal differentiation of the male genital organs; 5α-reductase deficiency syndrome; defective responsiveness of the testis to gonadotropin due to Leydig cell agenesis; various types of enzyme defects involved in testicular androgen biosynthesis; fetal testicular dysgenesis syndromes occurring at various stages of embryogenesis; and other less clearly defined entities of MPH. Implications are that other types of sexual differentiation disorders than MPH, such as true hermaphroditism, gonadal dysgenesis and some other disorders that have been considered to be distinct entities, may have close linkage to MPH through dysgenetic process of gonadal development with subsequent degeneration and/or tumorigenesis. Molecular basis of these probably related disorders should be elucidated in the near future and some clues to preventive measures for these genetically determined malformations are awaited.