Evidence for a direct anterior pituitary site of delta-9-tetrahydrocannabinol action

The effects of delta-9-tetrahydrocannabinol (THC), alone and in the presence of estradiol (E), on several estrogen-sensitive parameters in the immature female rat were examined, and it was demonstrated that THC administration antagonized the stimulatory effects of E on anterior pituitary weight and on both the secretion and pituitary content of prolactin. In the current study, the anterior pituitary gland was examined as a potential site of THC action in the ability of this cannabinoid to antagonize E-induced stimulation of pituitary function. A stimulatory dose of E (1 nM) significantly elevated prolactin levels in pituitary cells derived from either immature or retired breeder animals. Whereas THC (1 microM) alone had no effect on prolactin levels when compared to controls, THC completely prevented the E-induced increase in media prolactin levels. Moreover, THC blocked the ability of E to desensitize pituitary cells to the inhibitory influence of dopamine. Together with the findings that THC inhibited E-induced stimulation of total RNA synthesis in pituitary cell cultures, these data strongly suggest that THC antagonizes the stimulatory effect of E on the pituitary by a direct action at the adenohypophyseal level.