STEROID EXCRETION AND BIOSYNTHESIS, WITH SPECIAL REFERENCE TO 16-UNSATURATED C19 STEROIDS, IN CASES OF TESTICULAR FEMINIZATION AND IN A MALE PSEUDOHERMAPHRODITE

ABSTRACT The concentrations of the following steriods were measured in the urine of four patients with testicular feminization (TF) syndrome and of one male pseudohermaphrodite: 5α-androst-16-en-3α-ol (3α-androstenol), 5β-androst-16-en-3α-ol (aetiocholenol), 5,16-androstadien-3β-ol (androstadienol), androsterone, aetiocholanolone, dehydroepiandrosterone (DHA) and testosterone. Elevated levels of 3α-androstenol, androsterone, aetiocholanolone and DHA were found in the urine of two TF patients studied. The third TF patient and the male pseudohermaphrodite were excreting normal amounts for adult females of the three 16-unsaturated C19 steroids, although androgen output was raised. Decreases in the excretion of these steroids occurred after removal of the testes. Administration of human chorionic gonadotrophin (HCG) and corticotrophin (ACTH) to one TF patient resulted in two- to four-fold increases in urinary 16-unsaturated C19 steroids. The excretion of the three 17-oxosteroids measured, particularly androsterone and aetiocholanolone, increased after HCG and to a lesser extent after ACTH administration. In preparations of testes removed from three TF patients androstadienol (1-8%) was formed from pregnenolone. 4,16-Androstadien-3-one (androstadienone) was obtained in greater yield (0.2–1.33%) from progesterone than from pregnenolone (0.1–0.48%) although in the histologically normal testis from the pseudohermaphrodite, pregnenolone proved to be the more efficient precursor of androstadienone. Testosterone gave rise to no 16-unsaturated C19 steroids when incubated under identical conditions. The biosynthesis of testosterone in TF testis preparations was achieved normally from both pregnenolone and progesterone, in keeping with a defect in target organ insensitivity rather than in androgen formation. The possible significance of these findings and of the formation of large amounts (19%) of DHA from pregnenolone in TF testis is discussed.