Methods and results of aromatization studies in vivo.

In order to characterize aromatization in vivo, an androgen and an estrogen, labeled with different radioactive isotopes, are administered simultaneously, either as a pulse alone or as a pulse followed by a constant infusion of the same radiolabeled steroids. Subsequently, blood samples are obtained at varying time intervals and analyzed for the 3H/14C ratio in nonmetabolized unconjugated estrogen, and/or all urine is collected for 96 hr and analyzed for the 3H/14C ratio in an estrogen conjugate. The fraction of androgen (An) entering the blood which is converted to and measured as a specific estrogen (Es) in the blood ((P]BBEs)is calculated from (3H-Es/14C-Es)B (3H-An/14C-Es),„, where (3H-Es/14C-Es)B is the ratio of radioactivities in the specific estrogen in blood; (3H-An/14C-Es)lnj is the ratio of radioactivities administered. The fraction of androgen admin istered which is converted to a specific estrogen in the body and measured as a specific estrogen conjugate in the urine ([P]BMES) is calculated from (3H-Es/14C-Es)M (3H-An/'4C-Es>n, where (3H-An/14C-Es)M is the ratio of radioactivities in the specific estrogen conjugate. Irrespective of the method used, the aromatization of androstenedione is greater than the aro matization of testosterone; aromatization in normal men is greater than that in normal young women; aromatization in postmenopausal women is greater than that in premenopausal women. Aromatization occurs in many tissues but especially in adi pose tissue and muscle, and to a lesser extent in brain, kidney, and skin. The liver appears to be a relatively minor site for aromatization in normal subjects. In certain diseases, e.g., hepatic cirrhosis and obesity, aro matization rates are increased compared to those rates in normal individuals. In men and postmenopausal women, peripheral aromatiza tion of androgen is a major source of circulating estrogens. The peripheral aromatization of an androgen does not appear to be influenced by luteinizing hormone, follicle-stimulating hormone or adrenocorticotropic hormone or by substrate or product concentration. Blood flow through peripheral tissues may play a major role in control of this physiologically important reaction. Although there were indications from the early work of Leach et al. (10) that androgens could be aromatized to estrogens by peripheral extraglandular tissues, aromatization by these tis sues was not established until the work of MacDonald ef al. (18) and Longcope ef al. (15). These workers administered radiolabeled androgens to normal subjects and after extensive purification procedures found radiolabeled estrogens in the urine and blood. Studies since then have been directed at determining the importance of peripheral aromatization as a source of estrogens, the tissues involved in the reaction, dis ease states which alter the rate of aromatization, and the controlling mechanisms of the reaction. These studies have been carried out using analysis in either blood or urine, and I will review briefly the 2 techniques involved and then present and discuss the results.