Metabolism of dihydrotestosterone to 3α-androstanediol in brain and plasma: effect on behavioural activity in female rats

Abstract

ABSTRACT Six experiments were carried out to determine whether dihydrotestosterone (5α-androstan-17β-ol-3-one; DHT) acts to inhibit oestradiol (OE2)-induced lordosis behaviour after its metabolic conversion to 5α-androstane-3α,17β-diol (3α-androstanediol, 3α-Adiol). In experiments 1 and 2, ovariectomized rats were treated with several doses of DHT or 3α-Adiol, injected with OE2 and progesterone, and tested for lordosis responsiveness. Significant inhibition of lordosis occurred after a dose of 3α-Adiol which was approximately threefold less than the effective DHT dose. In experiments 3 and 4, plasma concentrations of DHT and 3α-Adiol were measured after the injection of these steroids to ovariectomized rats at doses shown to be both sufficient or insufficient to inhibit lordosis. Behaviourally effective dosages of DHT and 3α-Adiol produced circulating concentrations of 3α-Adiol greater than those produced by behaviourally ineffective doses of DHT or 3α-Adiol. At 30 min after injection of DHT (experiment 3), 78·8% of plasma androgens were in the form of 3α-Adiol, while after injection of 3α-Adiol, only 7·4% were DHT. When plasma DHT and 3α-Adiol were measured at 3, 6, 9 and 12 h after steroid injection (experiment 4), plasma levels of 3α-Adiol produced by the behaviourally subthreshold dose of DHT were significantly lower than levels produced by behaviourally sufficient dosages of DHT or 3α-Adiol. In experiments 5 and 6, concentrations of DHT and 3α-Adiol were measured in five brain regions 1 and 6 h after injection of behaviourally sufficient doses of these steroids to ovariectomized females. At 1 h after injection, similar levels of DHT and 3α-Adiol were measured in DHT- and 3α-Adiol-injected females, and DHT concentrations in the preoptic area were significantly higher in both groups than in any other brain area. At 6 h, animals injected with DHT had significantly higher levels of DHT in all brain areas combined than did 3α-Adiol-or vehicle-injected animals. Brain concentrations of 3α-Adiol were not different between groups injected with DHT, 3α-Adiol or vehicle at this time. In brain, 34·6% of DHT had been converted to 3α-Adiol after 1 h and 53·0% of 3α-Adiol had been converted to DHT. These results suggest that the inhibitory action of DHT on lordosis may be a consequence of its conversion to 3α-Adiol, and that this conversion may account for the higher behavioural potency of the latter steroid. Journal of Endocrinology (1992) 134, 183–195