In vivo studies on the metabolism of estrogens by muscle and adipose tissue of normal males.

3H and 14C-Labeled estrone, estradiol, and estrone sulfate were infused at constant rates into brachial arm veins of normal men. In any one experiment, subjects generally received two estrogens, one 3H-labeled and one 14C-labeled. During the infusions, blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In 11 men the mean +/- SE value for the metabolism of estrone by muscle, rho1,0A,M(rho1,0A,M = fraction of estrone in arterial blood which is metabolized by muscle) is 0.17 +/- 0.02 which is not (P greater than 0.1) significantly different from the mean +/- SE value for the metabolism of estrone by adipose tissue, rho1,0A,AT, 0.22 +/- 0.02. Both tissues convert estrone to estradiol, rho1,2A,M(rho1,2A,M = fraction of estrone in arterial blood which is measured as estradiol in venous blood draining muscle) is 0.026 +/- 0.005 and rho1,2A,AT is 0.022 +/- 0.005. Both tissues metabolized estradiol, rho2,0A,M = 0.09 +/- 0.01 and rho2,0A,AT = 0.12 +/- 0.03, and for each tissue the metabolism of estradiol was significantly less than that of estrone (P less than 0.01). Estradiol was converted to estrone by both tissues; rho2,1A,M = 0.007 +/- 0.003 and rho 2,1A,AT = 0.017 +/- 0.003. For estrone sulfate, tissue metabolism could be demonstrated in only 2 of 5 infusions; the values being 0.04 and 0.03, and 0.04 and 0.03 in muscle and adipose tissue, respectively. In only 1 of 3 infusions was evidence obtained for the conversion, by muscle, of estrone sulfate to estrone, rhoS,1A,M = 0.003 and only in one of the 5 subjects was adipose tissue active in this conversion. In no instance were we able to show conversion of estrone sulfate to estradiol by either tissue. In only 1 of 3 infusions could we measure demonstrable conversion of estrone to estrone sulfate by adipose tissue, rho1,SA,AT = 0.02, and we could not demonstrate conversion of estrone to estrone sulfate by muscle or of estradiol to estrone sulfate by either tissue. Both muscle and adipose tissue metabolize and interconvert the free estrogens, estrone and estradiol. The total metabolism by both tissues accounts for 5-10% of the overall metabolic clearance rate of each steroid. The formation of estrone sulfate from estrone and estradiol and the hydrolysis of estrone sulfate occurs to only a minor extent in these tissues.