Effects of cannabinoids and female exposure on the pituitary testicular axis in mice: Possible involvement of prostaglandins

Abstract

In immature (30-35-day-old) mice, a single dose of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of marihuana, decreased plasma testosterone (T), LH, and FSH levels, but the same dose of a nonpsychoactive component, cannabinol (CBN), had no effect. Chronic exposure to THC, CBN, or cannabidiol (CBD), beginning at 30 days of age through adulthood, influenced the endocrine responses to a sexually receptive female. Thus, weights of testes and seminal vesicles were reduced in males from all cannabinoid-treated groups on the day after exposure to a female, compared with treated males housed in all-male groups. Plasma FSH concentrations were elevated in CBN-exposed mice, regardless of social experience, while plasma T levels were increased after an encounter with a female in all but THC-treated males. Plasma LH levels and testicular responsiveness to gonadotropins in vitro were reduced in THC- and CBN-treated mice exposed to a female. In contrast, in THC- or CBN-treated males maintained in all-male groups, T production in vitro was significantly elevated. Alterations in prostaglandin (PG) concentrations may mediate these effects of cannabinoids and sexual encounter since production of PG in vitro by testis and pituitary was reduced by exposing cannabinoid-treated males to female-related stimuli. In contrast, sexual encounter increased PGF, but had no effect on PGE production by pituitary or testes obtained from oil-treated controls. Both psychoactive and nonpsychoactive constitutents of marihuana are capable of altering the function of the pituitary-gonadal axis and of influencing the endocrine responsivity to female-related exteroceptive cues in male mice.