Failure of 5α-Dihydrotestosterone to initiate Sexual Behaviour in the Castrated Male Rat

Abstract

IN most mammalian species the principal steroid product of the testes is testosterone, 17α-hydroxyandrost-4-en-3-one. In addition to being one of the most potent naturally occurring androgens it has been considered to be the active form of the hormone at target tissue level. Recent reports suggest, however, that a metabolite of testosterone, 17α-hydroxy-5-androstan-3-one (5α-dihydrotestosterone (5α-DHT)), may be the active form of the hormone^1,2. Several target organs (prostate, seminal vesicle and penis) rapidly convert testosterone to 5α-DHT (refs. 1 and 2). This conversion occurs before the attachment of the hormone to the receptors³ and seems to be essential for subsequent protein synthesis. Additional evidence for this function of 5α-DHT comes from studies on patients with testicular feminization; tissue biopsies from the genital organs of such patients cannot convert testosterone to 5KDNT (ref. 4). Testosterone can also activate both male and female sexual behaviour and is more potent than oestrogens in inducing libido in women⁵. Recently the enzyme system needed to convert testosterone to 5α-DHT has been demonstrated in the hypothalamus of the rat and dog^6,7, which suggests that 5α-DHT may also be the active form of testosterone in inducing sexual behaviour. In the ovariectomized female rabbit, however, 5α-DHT is devoid of any oestrus-inducing properties at doses from 2–20 mg per day⁸. 5α-DHT cannot be converted to oestrogenic metabolites in vivo⁹, which suggests that the aromatization of androgens may be of significance in the activation of sexual behaviour. This preliminary report concerns the failure of 5-DHT to initiate sexual behaviour in the castrated male rat.