Endocrinological problems in malformation of the male genitalia

There are two groups of congenital defects of the male genitalia: defects of organogenesis (e. g., aplasia of the external genitalia) and malformations due to defective hormonal influences on these organs. The pathophysiological mechanisms of the functional malformations can be a defect of androgen biosynthesis in the gonads, defects of conversion of precursor hormones into the biologically active compound, and defects at the receptor site with a faulty hormonal utilisation. All these defects in the production of a biologically active substance can be present and operating very early in life, i. e., in the embryonal or foetal period. Problems can arise from the mother and particularly the placenta, or from the child (pituitary). The production of an antimüllerian hormone in Sertoli cells has been recently reported as an additional important mechanism. These hormonal defects influence the development of the male genitourinary tract system. Testosterone biosynthesis has several enzymatic steps: The synthesis of androgens starts early in the embryonal period, with the final transformation of the indifferent organ into the differentiated external male genitalia occurring under the influence of the foetal testosterone. Targets for these hormonal malfunctions are, besides the urogenital system, an enzyme (5-alpha-hydroxylase) and cytoplasmic and nuclear receptor sites on the skin of the external genital region. One of the clinical manifestations of such a hormonal malfunction is a defective virilisation of the external male genitals, with several types of hypospadias. Complete and partial defects of testosterone biosynthesis are known. Extensive laboratory investigations disclose the specific defect. Besides hypospadias, similar malformations occur in the form of ambiguous external genitalia if testosterone cannot metabolize into dihydrotestosterone in the target cell. In earlier descriptions this congenital genitourinary defect was called pseudovaginal perineoscrotal hypospadias. Today, the specific defect is identified as a 5-alpha-reductase deficiency. The diagnosis is established by a skin biopsy of the genital area. Ambiguous genitalia of variable expression are present if the receptor sites at the target cells are defective. The clinical presentation is known as testicular feminization or hereditary male pseudohermaphroditism. Incomplete partial expression of this disorder is known. The diagnosis is made clinically, and diagnosis is proven by investigation of hormone receptor sites in the target cells in the skin of the genital region.(ABSTRACT TRUNCATED AT 400 WORDS)