Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors

Abstract

The aim of our study was to establish the definitive diagnosis in an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the age of 8, based on genetic, clinical and pathological studies. Hypothalamo-hypophysio-testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro. At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid. LH and FSH were determined pre- and post-gonadectomy. Progesterone, 17-OH-progesterone, androstenedione, dehydroepiandrosterone testosterone (T) and oestradiol were determined basally in peripheral and spermatic blood post-hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5 alpha-reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Leydig-like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5 alpha-reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27.0 vs 9.4 +/- 0.6 fmol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low. The patient was considered to have an almost complete form of Leydig cell agenesia/hypoplasia in which absence of specific LH binding correlated with total absence of differentiated Leydig cells and insensitivity of undifferentiated interstitial cells to LH stimulation.