Lipoidal Derivative of Estradiol: The Biosynthesis of a Nonpolar Estrogen Metabolite*

Abstract

The incubation of estradiol with human breast tumors as well as several estrogen-responsive tissues of the rat, including dimethylbenzanthracene-induced mammary tumors, leads to the formation of a nonpolar metabolite. This compound has been called a lipoidal derivative of estradiol because of its nonpolar characteristics and because it is converted back into estradiol with alkali. The properties of this metabolite are similar to those of the endogenous lipoidal derivatives of the Δ⁵-3βhydroxysteroids, pregnenolone, 17-hydroxypregnenolone, and dehydroisoandrosterone, that were found in the adrenal. When estrone was incubated in a similar manner, a nonpolar metabolite was formed, but it was the lipoidal derivative of estradiol, not estrone. The lipoidal derivative of estradiol was not oxidized by treatment with CrO₃, which showed that the lipoidal moiety is linked to the C-17 of the steroid nucleus. Unlike other estrogen metabolites, the lipoidal derivative of estradiol is found only within the tissue and cannot be detected in the incubation medium.