Levels of plasma C19 steroids and 5 alpha-reduced C19 steroid glucuronides in primates, rodents, and domestic animals.

Abstract

In this study, a comparison of circulating levels of androsterone glucuronide and androstane-3 alpha, 17 beta-diol glucuronide in the male and female of several mammalian species was performed. Glucuronidated steroids were not detected in the circulation of the dog, bovine, swine, and rodent. High levels of circulating glucuronidated steroids were measured in the cynomolgus monkey and found to be 10-fold higher than in humans. The determination of tissue levels of unconjugated and conjugated C19 steroids was then performed in intact and castrated rats treated with androgens. Steroid glucuronides were not detected in the plasma, skin, prostate, or liver of either intact or treated rats, although the levels of unconjugated steroids in the plasma and tissues were increased after steroid treatments. Significant levels were detected in the bile, thus suggesting hepatic formation of steroid glucuronides in the rat. It is suggested that the monkey represents the best animal model to date to study the contribution of diphosphoglucuronosyltransferases present in steroid target peripheral tissues to circulating levels of steroid glucuronides.