DELTA-9-TETRAHYDROCANNABINOL ANTAGONISM OF THE ANTERIOR-PITUITARY RESPONSE TO ESTRADIOL IN IMMATURE FEMALE RATS

The potential estrogenicity or antiestrogenicity of DELTA-9-tetrahydrocannabinol (THC), the chief psychoactive constituent of marijuana, was evaluated in immature female rats treated for 3 days with estradiol (E2; 1-mu-g/kg), THC (10 mg/kg body weight) or E2 + THC. Estradiol treatment significantly increased anterior pituitary, uterine, and oviduct weights. When THC was administered with E2, it prevented the E2-induced increase in pituitary weight, but had no effect on either the uterine or oviduct weight response to E2. In the E2 treatment group, basal prolactin levels were increased and a prolactin surge occurred on the afternoon of the 26th day of age. However, E2-stimulated basal and surge levels of prolactin were significantly attenuated by concomitant THC treatment. Moreover, pituitary prolactin concentrations, which were elevated in E2-treated rats, did not differ from control values in E2 + THC-treated animals. The E2-induced decrease in dopamine turnover rates in the medial basal hypothalamus and increase in the number of anterior pituitary dopamine D-binding sites (B(max)) were not affected by concomitant THC treatment. Thus, THC antagonizes E2 action on the anterior pituitary via yet to be elucidated mechanism(s).