22 STEROID BIOSNTHESIS IN PATIENTS WITH MALE PSUDOHERMAFRODITISM. STUDIES PERFORMED IN LEYDIGG CELL MESENCHYMAL PRECURSORS IN CULTURE

Abstract

Among the cause of male pseudohermafroditism(MPH), disorders of testicular function, which include enzymatic defects in the testosterone (T)biosynthesis, have been demonstrated. In a 8 1/2 years old patient with MPH (MG, 46 XY), with ambiguous genitalia and raised as a female, plasmatic levels of the following steroids were determined: Pregnenolone (P5), Progesterone (P4), Androstenedione (Δ 4), 17αhydroxyprogesterone (17αOHP4) and T. Values were found in the normal prepubertal range. Lack of response to acute hCG stimulation for these steroids was observed. After gonadectomy, Leydig cell mesenchymal precursors were isolated as previously described (Biol.Reprod.46:793, 1992). Cells were cultured for 6 days and T,P5,P4 17OHP4, Δ4 and dehydroepiandrosterone (DHA) levels were determined by RIA in the culture medium. Results were compared with those found in two other patients (PM, VT) bearing the androgen insensitivity syndrome. Levels of T (pg/h/ugDNA) were as follows, MG:0.35±0.06, PM:101±10 and VT: 141±15. Similar results in FSH or hCG stimulated cultures were obtained. The overall steroid production in the three patients was: MG: 108, PM; 184 and VT: 319 (pg/h/ugDNA). A marked modification of T/Δ 4 relationship was observed in MG (MG: 0.03, PM: 64 and VT: 3.97). These results suggest that MG male pseudohermafroditism is due to 17β hydroxysteroid dehydrogenase deficiency. This deficiency could not be demonstrated at the peripheral level but it was evident in Leydig cell mesenchymal precursors in culture.