ACTION OF HORMONES ON PROTEIN AND RNA METABOLISM

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To explore the mechanisms by which androgens act to induce masculinization of the male urogenital tract during embryogenesis and to virilize the male at the time of puberty and to provide insight into the pathogenesis of abnormal sexual development, a variety of experiments are planned. These include investigation in cultured skin fibroblasts of the molecular defects in the androgen receptor responsible for androgen resistance states associated with male pseudohermaphroditism, study of the pathogenesis of steroid 5 alpha-reductase deficiency and of the regulation of 5 alpha-reductase activity in target tissue, investigation of the role of dihydrotestosterone formation in androgen physiology using inhibitors of 5 alpha-reductase activity, characterization of the androgen receptor machinery in embryonic tissue, investigation of the endocrine differentiation of gonads by which chromosomal sex is ultimately transplanted into phenotypic sex, and a genetic and enzymatic characterization of the aromatase reaction by which androgens are converted to estrogens in peripheral tissues, using tissues and fibroblasts from normal and henny feathered chickens and from patients with a variety of pathological states. Thus, a multifaceted approach is projected to provide insight into androgen metabolism and action in the normal and into the pethophysiology of normal sexual development as well.