Metabolism of Steroids in Germfree and Conventional Rats Treated with a 3β‐Hydroxy‐δ⁵‐Steroid Oxidoreductase Inhibitor

The 3β‐hydroxy‐Δ⁵‐steroid oxidoreductase inhibitor 2α‐cyano‐4,4,17α‐trimethyl‐5‐androsten‐17β‐ol‐3‐one was administered intramuscularly to germfree and conventional, male and female, rats. Under the experimental conditions used, no steroids were found in faeces and urine from the male rats, but a large number of steroids were identified in excreta from female rats. The following 3β‐hydroxy‐Δ⁵‐steroids, none of which is present in normal rats, appeared in urine and faeces from germfree and conventional cyanoketone treated female rats (chiefly as mono‐sulphates): 5‐androstene‐3β, 17β‐diol, 3β, 7α(and 7β)‐dihydroxy‐5‐androsten‐17‐one, 5‐androstene‐3β, 7α(and 7β), 17β‐triol, 3β, 16α‐dihydroxy‐5‐androsten‐17‐one, 3β, 17β‐dihydroxy‐5‐androsten‐16‐one, 3β‐hydroxy‐5,16‐pregnadien‐20‐one, 3β‐hydroxy‐17α‐pregn‐5‐en‐20‐one, 3β‐hydroxy‐5‐pregnen‐20‐one, 3β,7α(and 7β)‐dihydroxy‐5‐pregnen‐20‐one, 3β, 17α‐dihydroxy‐5‐pregnen‐20‐one, 3β, 16β‐dihydroxy‐5‐pregnen‐20‐one, 5‐pregnene‐3β, 16α, 20α‐triol, 5‐pregnene‐3β, 17α, 20α‐triol and 3β, 21‐dihydroxy‐5‐pregnen‐20‐one. In addition, several saturated steroids were identified which were identical with steroids excreted by normal germfree and conventional female rats. 3β, 16α‐Dihydroxy‐5‐pregnen‐20‐one normally accounts for less than 1% of the total amount of 3β, 16α‐dihydroxy‐5‐pregnen‐20‐one and 3α, 16α‐dihydroxy‐5α‐pregnan‐20‐one found in urine. This percentage was found to be about 70–80 in urine from cyanoketone treated germfree as well as conventional female rats. This figure is in good agreement with the extent of inhibition (75–85%) of adrenal and gonadal (testicular and ovarian) 3β‐hydroxy‐Δ⁵‐steroid oxidoreductase found in experiments in vitro. It was established that the formation of saturated steroids from 3β‐hydroxy‐Δ⁵‐steroids in cyanoketone treated rats involved 3‐oxo‐steroids as intermediates since [3α‐³H,4‐¹⁴C]pregnenolone was converted into saturated steroids with loss of ³H. The hepatic 3β‐hydroxy‐Δ⁵‐steroid oxidoreductase active on C₂₇ steroids was unaffected by treatment in vivo or in vitro with the cyanoketone.