In vitro and in vivo studies on the metabolism of estrogens and their sulfates in guinea pigs

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Abstract
Labeled estradiol-17.beta.(E2) or estrone (E1), when incubated with guinea pig liver slices, is metabolized by 2 main pathways. Part of each substrate is converted to estrone-3-glucuronide and estradiol-3-glucuronide. A further part of each is metabolized to estradiol-3-sulfate (E23S) and estrone-3-sulfate (E13S), which are interconverted. The latter conjugate appears to be the substrate for a 16.alpha.-hydroxylase forming 16.alpha.-hydroxyestrone-3-sulfate (16.alpha.OHE13S). This is further sulfurylated to yield 16.alpha.-hydroxyestrone-3,16-sulfate, accompanied by estriol-3,16-disulfate. A relatively small amount of tentatively identified 6-hydroxyestrone disulfate accompanies these other 2 diconjugates. The guinea pig liver system suggests itself as a useful and relatively simple model for further study of 16.alpha.-hydroxylation of E23S. The use of the latter as a natural substrate in the system in vitro is supported by the observation that E23S and E23S are present in liver, kidney, blood, gallbladder bile, intestine, uterus and placenta after injection of labeled E2 into mature male and female guinea pigs. Some evidence was obtained for the disulfate fraction (above) in liver and bile after injection of labeled E1.