Acute delta 9-tetrahydrocannabinol exposure: effects on hypothalamic-pituitary-testicular activity in mice

Abstract

The endocrine functions of the median eminence, pituitary and testes were examined in male mice after exposure to delta 9-tetrahydrocannabinol (THC) either in vivo or in vitro. The secretion of luteinizing hormone-releasing hormone (LHRH) under basal conditions, and in the presence of norepinephrine (NE; 60 microM), was significantly enhanced in median eminence fragments obtained 1 hr post-treatment with THC (50 mg/kg), while addition of THC (250 ng/ml) to the incubation media enhanced clonidine, as well as NE-stimulated LHRH release, but did not affect basal LHRH release. In vitro exposure to THC also enhanced LHRH-stimulated LH release by pituitaries, but did not affect basal secretion rates. In vivo THC exposure tended to enhance pituitary responsiveness to LHRH, although this effect was not statistically significant. In testicular perifusions, addition of THC at a concentration of 250 ng/ml completely blocked hCG-stimulated T secretion within 30 min. The suppressive effects of a lower dose of THC, 25 ng/ml, required 60 min to inhibit T production, an effect which persisted for 60-80 min post-THC. These findings indicate that THC exposure enhances responsivity at neuroendocrine target sites, but attenuates gonadotropin-stimulated testicular steroidogenesis.