FROM ENDOCRINOLOGY TO INTRACRINOLOGY

Recently, in situ formation of active sex steroids at the sites of the ir actions from biologically inactive precursors in the circulation ha ve been demonstrated to play very important roles in sex steroid-depen dent neoplasms. These tissues in which the conversion occurs are desig nated as intracrine tissues and their mechanisms of actions can be des ignated as intracrinology in contrast to endocrinology. Aromatase, whi ch converts serum androgens to estrone, and 17 beta-hydroxysteroid deh ydrogenase I, which is involved primarily in the conversion of estrone to estradiol, are two major enzymes which function in the in situ for mation of biologically active estrogens from circulatory androgens. In human estrogen-dependent neoplasms, including breast, endometrioid en dometrial, and common epithelial ovarian carcinoma, we recently demons trated overexpression of aromatase, especially in stromal cells at sit es of frank invasion possibly under a new promoter usage and that of 1 7 beta-hydroxysteroid dehydrogenase I in these carcinoma cells. These estrogen-dependent carcinomas are considered to have a common characte ristic in estrogen metabolism (i.e., the expression of aromatase in th e stroma I cells and of 17 beta-hydroxysteroid dehydrogenase I in the epithelial cells). With these in situ mechanisms of generating biologi cally active estrogens from circulating androgens, that is, ''intracri ne manner,'' these estrogen-dependent neoplasms can exert estrogenic a ctions on carcinoma cells despite low circulating serum estrogen level s, as observed in postmenopausal women. Evaluation of intracrine mecha nisms can provide new insights into various estrogen-related biologica l phenomena in humans.