Effects of 9-ene-tetrahydrocannabinol on uterine estrogenicity in the mouse

Abstract

Several early (Phase I) and late (Phase II) estrogenic effects of 9-ene-tetrahydrocannabinol (THC) were examined in the adult mouse uterus. An injection of THC (2.5 or 10 mg/kg body wt) in ovariectomized mice neither stimulated uterine water imbibition or accumulation of [ 125I]bovine serum albumin (Phase I responses) at 6 h, nor antagonized these Phase I responses elicited by estradiol-17β (E 2). With respect to Phase II responses, although single injections of THC (2.5, 5.0 and 10 mg/kg body wt) alone were ineffective in influencing uterine weight at 24 h or incorporation of [ 3H]thymidine at 18 h, this drug interfered with these responses elicited by E 2 in a dose-dependent manner. In contrast, an injection of THC in progesterone (P 4)-primed ovariectomized mice modestly enhanced (61%) uterine incorporation of [ 3H]thymidine. However, E 2-stimulated uterine thymidine incorporation in P 4-primed ovariectomized mice was antagonized by THC treatment. Effects of THC on blastocyst implantation were examined. Single or multiple injections of various doses of THC neither induced implantation in P 4-primed delayed implanting mice, nor interfered with E 2-induced implantation. Furthermore, daily injections of THC (10 mg/kg body wt) during the periimplantation period had no apparent adverse effects on implantation, or on experimentally induced decidualization (deciduomata). The data suggest that THC is neither pro- nor antiestrogenic with respect to Phase I responses. However as regards Phase II responses, THC is modestly proestrogenic in the P 4-treated uterus, but is antiestrogenic in the presence of E 2. These estrogen agonistic/antagonistic effects of THC on uterine Phase II responses do not adversely affect the process of implantation and decidualization.