GESCHLECHTSSPEZIFIKA DER BIOSYNTHESE VON STEROIDGLUCURONIDEN IN DER MIT TESTOSTERON PERFUNDIERTEN RATTENLEBER

Abstract

ABSTRACT In order to reveal contingent sex specificities regarding the biosynthesis of steroid glucuronides perfusion experiments with rat liver and [4-14C] testosterone** as substrate were carried out. 75% (male rats) respectively 89% (female rats) of the chromatographically isolated aglucones could be identified. In the course of one single passage of the substrate the female liver retains significantly more (factor 1.4) 14C-activity than the male. Since this phenomenon is not due to a sex different capacity of the liver for the synthesis of steroid glucuronides, it must be regarded as a sex characteristic sui generis. The aglucone pattern exhibits the following sex differences: The quantitatively predominant aglucones are testosterone (47%) and hydroxylated Δ4-3-ketosteroids in male rats and ring A hydrogenated products of the type C19O2 (80.7%) in females. Within the group of ring A hydrogenated C19O2-aglucones the biologically inactive 5β-compounds (5β-androsterone, 17β-hydroxy-5β-androstan-3-one, 5β-androstane-3α, 17β-diol) prevail in the male sex, and the biologically active 5α-compounds (5α-androsterone, 17β-hydroxy-5α-androstan-3-one, 5α-androstane-3α, 17β-diol) in the female sex. With either sex the percentage share of 5α- and 5β-androsterone and 5α- and 5β-androstane-3α,17β-diol in the glucuronide fraction is extremely higher than in the fraction of free steroids though the affinity of the UDP-glucuronyl transferase of the rat liver is considerably lower for these four metabolites than for the 4,5-dihydro-testosterone derivatives which, however, for their part are nearly equally distributed between the glucuronide and the free steroid fraction. Therefore, it can be postulated that the glucuronides of the above mentioned androsterones and androstanediols derive mainly from the hydrogenation of testosterone glucuronide and only for the minor part from direct conjugation of the hydrogenation products with glucuronic acid.