Effects of delta 9-THC and castration on behavior and plasma hormone levels in male mice

Gonadectomy resulted in a rapid increase in plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, but had no consistent effects on plasma prolactin (PRL) and growth hormone (GH) levels. In castrated males, oral administration of THC (50 mg/kg) significantly increased plasma LH levels within hours following surgery and again from 3 to several weeks post-castration, while THC treatment decreased LH levels between 1 day and 2 weeks postcastration. Administration of THC to 12-hour sham castrates significantly increased plasma LH levels. Plasma FSH, PRL and GH levels were either reduced or unchanged by THC. Administration of THC significantly reduced levels of gonadotropins, PRL and GH in intact males. In additional studies, we examined the influence of THC on the negative feedback response of the anterior pituitary to gonadal steroids. In testosterone propionate (TP)-treated castrated males, concomitant administration of THC increased plasma testosterone (T) and LH at 20 min, while plasma FSH levels were elevated after 60 min. In contrast, in intact TP-treated mice, concomitant THC exposure reduced plasma T levels except at 60 min, when plasma LH levels were significantly increased. Testosterone replacement failed to restore copulatory behavior in castrated mice given a single dose (50 mg/kg) of THC. In fact, acute THC administration to these TP-treated castrates resulted in marked sedation, which was not observed in intact mice given the same dose of THC in an earlier study. The present findings indicate that the effects of acute THC treatment on pituitary gonadotropin release is dependent upon the time after castration. Furthermore, THC administration can suppress copulatory behavior even in animals whose peripheral T levels have been maintained. Effects of THC on plasma androgen levels in animals injected with TP suggest that THC can alter the metabolism or target tissue response to gonadal steroids.