Effects of cannabinoids on progesterone release in cultures of rat luteal cells.

This study investigated the direct effects of tetrahydrocannabinols (THC) on progesterone release by cultured rat luteal cells, as a function of dose and time. During a 24-h incubation, the level of progesterone in the culture medium was decreased by 35% and 60% in the presence of 1 microM 11-OH-delta 9-THC and 8 beta-OH-delta 9-THC, respectively, when compared with control cultures. Dose-response analysis revealed that 8 beta-OH-delta 9-THC inhibited progesterone levels at 0.1 microM but not at lower concentrations. The action of 8 beta-OH-delta 9-THC was rapid in onset and a significant effect could be observed as early as 2 h following the addition of the cannabinoid. While luteinizing hormone (LH, 1 microgram/ml) significantly enhanced progesterone release in the culture medium over the respective control levels, this action of LH was dramatically suppressed by the concomitant presence of 8 beta-OH-delta 9-THC at 2, 4 and 24 h in separate experiments. Moreover, the increase in the level of progesterone in the culture medium induced by 8-bromo-cyclic AMP was also attenuated by the concomitant presence of 8 beta-OH-delta 9-THC in the cultures. These results further substantiate a direct action of cannabinoids on the steroidogenic function of the corpus luteum, and that it involves at least some step(s) distal to the LH-sensitive adenylate cyclase system.