Effects of chronic treatment with delta-9-tetrahydrocannabinol on uterine growth in the mouse

The estrogenic responses of delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, remain unsettled. We examined the effects of chronic treatment of THC on uterine wet weights and nuclear 3H-thymidine incorporation (DNA synthesis), and compared these responses with those of an acute treatment of estradiol-17 beta (E2) in ovariectomized (OVX) or hypophysectomized (HYPOX) mice. As shown previously, an injection of E2 increased uterine weights and nuclear 3H-thymidine incorporation in epithelial cells in OVX or HYPOX mice when examined 18 h after the injection. Injections of THC daily for 7 days also elicited uterine weight gains and nuclear 3H-thymidine incorporation in a dose dependent manner in OVX or HYPOX mice as compared to the vehicle (oil) treated controls. Like E2, THC induced nuclear 3H-thymidine incorporation primarily in luminal and glandular epithelial cells. However, effects of THC in these responses were much inferior to those elicited by an injection of E2. These data suggest that THC, given chronically in the mouse, behave as a weak uterotrophic agent, and THC effects are not mediated by the pituitary.