COMPARISON OF IMMUNOCYTOCHEMICAL AND MOLECULAR-FEATURES WITH THE PHENOTYPE IN A CASE OF INCOMPLETE MALE PSEUDOHERMAPHRODITISM ASSOCIATED WITH A MUTATION OF THE LUTEINIZING-HORMONE RECEPTOR

We report the case of an infant who presented at birth with a hypoplas tic phallus associated with hypospadias. Low testosterone production, normal serum levels of steroid precursors, and increased LH in respons e to LH-releasing hormone supported a defect in Leydig cell differenti ation or function. Conventional microscopic study of the testes showed fibroblastic cells in the interstitium. However, immunocytochemical a nalysis using anti-LH receptor and anti-P450c17 antibodies demonstrate d that about one third of these cells were Leydig cells or precursors of Leydig cells. No histological feature could distinguish the latter cells from fibroblasts. A homozygous substitution of cysteine 133 for arginine was found in the extracellular domain of the receptor. This i s the first naturally occurring missense mutation found in the extrace llular domain of the LH receptor. COS-7 cells transfected with the mut ant receptor exhibited a marked impairment of hCG binding, whereas som e cAMP production could be observed at high hCG concentrations. We pro pose that the partial impairment of LH receptor function, as reflected by the presence of Leydig cells, was responsible for the incomplete m ale pseudohermaphroditism observed in our patient.