Δ 9-Tetrahydrocannabinol antagonism of the anterior pituitary response to estradiol in immature female rats

Abstract

The potential estrogenicity or antiestrogenicity of Δ 9-tetrahydrocannabinol (THC), the chief psychoactive constituent of marijuana, was evaluated in immature female rats treated for 3 days with estradiol (E 2; 1 μg/kg), THC (10 mg/kg body weight), or E 2 + THC. Estradiol treatment significantly increased anterior pituitary, uterine, and oviduct weights. When THC was administered with E 2, it prevented the E 2-induced increase in pituitary weight, but had no effect on either the uterine or oviduct weight response to E 2. In the E 2 treatment group, basal prolactin levels were increased and a prolactin surge occurred on the afternoon of the 26th day of age. However, E 2-stimulated basal and surge levels of prolactin were significantly attenuated by concomitant THC treatment. Moreover, pituitary prolactin concentrations, which were elevated in Entreated rats, did not differ from control values in E 2 + THC-treated animals. The E 2-induced decrease in dopamine turnover rates in the medial basal hypothalamus and increase in the number of anterior pituitary dopamine D 2-binding sites (B max) were not affected by concomitant THC treatment. Thus, THC antagonizes E 2 action on the anterior pituitary via yet to be elucidated mechanism(s).