Studies on Testosterone Metabolism in Human Subjects with Normal and Pathological Sexual Differentiation

Abstract

Normal individuals and subjects with abnormalities of sex differentiation have been injected with radioactive traces of testosterone and 17β-hydroxy-5α-androstan-3-one. These experiments have been done in order to compare the contribution of both precursors to urinary 17-oxo- and 17β-hydroxyandrostane steroids. In females as in boys before puberty a great part of injected testosterone seems to be oxidized to androstenedione. By contrast, the direct reduction of testosterone to 5α- and 5β-androstanediols is relatively important in males after puberty. When gonads are absent as in Turner's syndrome, or deficient as in hypogonadal males, the Δ4-reduction of testosterone remains very weak. However, if hypogonadism is owing to a pituitary deficiency, chorionic gonadotrophin restores a normal male metabolic pattern. In all these situations, the yield of metabolites formed through the 17β-hydroxy pathway of testosterone seems to correlate with the amount of this androgen in biological fluids. This is not the case in patients with testicular feminization syndrome, in whom, despite normal male testosterone secretion, the conversion of testosterone and 17β-hydroxy-5α-androstan-3-one to androstanediols occurs at a very low rate. The possible relationship between the appearance of male sexual differentiation and the stimulation of enzymes allowing ring A reduction of testosterone is discussed.