Leung P C, Flesher M, Moon Y S, Minegishi T
Life Sci. 1985 Nov 4;37(18):1691-6. doi: 10.1016/0024-3205(85)90296-6.
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.
本研究调查了四氢大麻酚（THC）对培养的大鼠黄体细胞孕酮释放的直接影响，该影响是剂量和时间的函数。在24小时的孵育过程中，与对照培养相比，在存在1 microM 11-羟基-Δ9-THC和8β-羟基-Δ9-THC的情况下，培养基中孕酮水平分别降低了35%和60%。剂量反应分析表明，8β-羟基-Δ9-THC在0.1 microM时抑制孕酮水平，但在较低浓度时则无此作用。8β-羟基-Δ9-THC的作用起效迅速，早在添加大麻素后2小时即可观察到显著效果。虽然促黄体生成素（LH，1微克/毫升）使培养基中孕酮释放相对于各自对照水平显著增强，但在单独实验中，在2、4和24小时时，8β-羟基-Δ9-THC的同时存在显著抑制了LH的这一作用。此外，培养物中8-溴环磷酸腺苷诱导的培养基中孕酮水平升高也因8β-羟基-Δ9-THC的同时存在而减弱。这些结果进一步证实了大麻素对黄体类固醇生成功能有直接作用，且该作用至少涉及LH敏感腺苷酸环化酶系统下游的某些步骤。
