STUDIES ON INACTIVATION OF ESTRADIOL BY THE LIVER1

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Abstract
Little or no active estrogen can be recovered from the liver of the dog 3-48 hrs. after intraven. injn. of a-estradiol. 24 and 48 hrs. after injn., large amts. are present in the gall-bladder bile, but none in the liver, spleen, intestine and hepatic vein blood. In 1 of 3 expts. there was a relatively high conc. of estrogen in the portal vein blood. The livers of rats poisoned with CCl4 exhibit essentially the same capacity as normal liver for inactivating estradiol in vitro. These observations do not support the hypothesis that the increased activity of endogenous and exogenous estrogen in the presence of hepatic damage is due to decreased inactivation of estrogen by the damaged liver cells. The following hypothesis is in accord with all available data: Estrogen is removed from the blood by the liver cells, is converted to a substance possessing little or no estrogenic activity, is in part stored temporarily in the liver in this form, and is "reactivated" during the process of its excretion by the hepatic cells. The estrogen probably undergoes an enterohepatic circulation similar to that of bile acids, being perhaps gradually destroyed or converted to a permanently inactive substance.