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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Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Biochemical Endocrinology Study Section (BCE)
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Weill Medical College of Cornell University
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New York
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Sobel, Vivian; Schwartz, Brian; Zhu, Yuan-Shan et al. (2006) Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes. J Clin Endocrinol Metab 91:3017-23
Imperato-McGinley, J; Zhu, Y-S (2002) Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol 198:51-9
Zhu, Y S; Cai, L Q; Cordero, J J et al. (1999) A novel mutation in the CAG triplet region of exon 1 of androgen receptor gene causes complete androgen insensitivity syndrome in a large kindred. J Clin Endocrinol Metab 84:1590-4
Can, S; Zhu, Y S; Cai, L Q et al. (1998) The identification of 5 alpha-reductase-2 and 17 beta-hydroxysteroid dehydrogenase-3 gene defects in male pseudohermaphrodites from a Turkish kindred. J Clin Endocrinol Metab 83:560-9
Zhu, Y S; Katz, M D; Imperato-McGinley, J (1998) Natural potent androgens: lessons from human genetic models. Baillieres Clin Endocrinol Metab 12:83-113
Cai, L Q; Zhu, Y S; Katz, M D et al. (1996) 5 alpha-reductase-2 gene mutations in the Dominican Republic. J Clin Endocrinol Metab 81:1730-5
Katz, M D; Cai, L Q; Zhu, Y S et al. (1995) The biochemical and phenotypic characterization of females homozygous for 5 alpha-reductase-2 deficiency. J Clin Endocrinol Metab 80:3160-7
Mendez, J P; Ulloa-Aguirre, A; Imperato-McGinley, J et al. (1995) Male pseudohermaphroditism due to primary 5 alpha-reductase deficiency: variation in gender identity reversal in seven Mexican patients from five different pedigrees. J Endocrinol Invest 18:205-13
Canovatchel, W J; Volquez, D; Huang, S et al. (1994) Luteinizing hormone pulsatility in subjects with 5-alpha-reductase deficiency and decreased dihydrotestosterone production. J Clin Endocrinol Metab 78:916-21
Cai, L Q; Fratianni, C M; Gautier, T et al. (1994) Dihydrotestosterone regulation of semen in male pseudohermaphrodites with 5 alpha-reductase-2 deficiency. J Clin Endocrinol Metab 79:409-14

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