The purpose of this investigation is to define the mechanisms, determinants, and physiologic and pathophysiologic significance of extraglandular estrogen production. Of principal importance is to determine the extent of conversion of plasma androstenedione to the product hormone, estrone, in women and men; and, further, to define the extent of conversion of plasma testosterone to estradiol-beta 17 in men. Estrogen production in postmenopausal women, children, and men is derived primarily from the utilization of preformed plasma steroids which are converted to estrone and estradiol-beta 17 at site(s) other than the adrenal, testes, or ovary. Furthermore, during the course of childhood, there is a profound decrease in the capability for extraglandular aromatization of preformed steroidal precursors. During fetal life and in the newborn period, there is massive aromatization of plasma precursors for estrogen production. This capability, as expressed per pound of body weight, progressively decreases until the just pre-pubertal period. Thereafter, during young adulthood, the extent of aromatization of plasma precursors remains relatively stable unless affected by significant increases in body weight or liver disease. Thereafter, with aging, there is a considerable increase in the extent of aromatization of plasma precursors. The purpose of this project is to define the mechanisms which control extraglandular aromatization of plasma precursors and to investigate the physiologic and pathophysiologic significance of extraglandular estrogen production as it may relate to the onset of puberty, and various androgen-estrogen endocrinopathies that include gynecomastia, endometrial carcinoma, and anovulation. BIBLIOGRAPHIC REFERENCES: MacDonald, P. C., J. M. Grodin, C. D. Edman, F. Vellios, and P. K. Siiteri: Origin of Estrogen in a Postmenopausal Woman with a Nonendocrine Tumor of the Ovary and Endometrial Hyperplasia. Obstet. Gynecol., 47:644 1976. MacDonald, P. C., C.D. Edman, I.J. Kerber, and P.K. Siiteri: Plasma Precursors of Estrogen: III. Conversion of Plasma Dehydroisoandrosterone to Estrogen in Young, Nonpregnant Women. Gynecol. Invest., 7:165, 1976.