We will continue studies of a clinically distinct inherited form of male pseudohermaphroditism due to 5 alpha-reductase deficiency in a large group (33 living affected males) of individuals from the Dominican Republic. We plan to complete the pedigree of the families with 5 alpha-reductase deficiency and to calculate the coefficient of inbreeding and the gene frequencies in this geographic isolate. The decreased urinary excretion of 5 alpha-reduced metabolites of testosterone (T) is useful for carrier detection, however assay of other steroid metabolites may serve as a more sensitive method for detection of heterozygotes. Preliminary results show that 5 alpha-reduced metabolites of other delta 4-3 ketosteroids are also diminished, suggesting that the gene controlling 5 alpha-reduction of T is the same as that catalyzing the corresponding reduction of other naturally secreted steroids. We are looking at factors involved in gender identity, and psychosexual development in the subjects with 5 alpha-reductase deficiency. Also, the role of 5 alpha-dihydrotestosterone (DHT) in regulation of the gonadotropin secretion in normal males, 5 alpha-reductase deficient males, and subjects with testicular feminization, by comparing response of plasma LH, FSH, T, androstenedione, and 17 alpha hydroxyprogesterone to continuous infusion of DHT at different dose levels. We have also initiated a series of studies of a large family of individuals with male pseudohermaphroditism due to testicular feminization (17 living adults). We will evaluate a large number of sporadic and familial cases of other forms of male pseudohermaphroditism that have a phenotype similar to individuals with 5 alpha-reductase deficiency.
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