Lewysohn O, Cordova T, Nimrod A, Ayalon D
Horm Res. 1984;19(1):43-51. doi: 10.1159/000179858.
In previous study the major psychoactive ingredient of marihuana (delta 1-THC) has been shown to inhibit ovarian prostaglandin synthesis when administered to normally cycling rats in the early afternoon of proestrus. These results suggested a direct suppressive effect of the drug on the ovary. The purpose of this study was to evaluate the effect of delta 1-THC on steroidogenesis in granulosa cells (GC) in vitro. Incubation of GC with delta 1-THC (10-50 microM) effectively inhibited LH-stimulatable progestin production. This suppressive effect was not abolished by washing the cells after 24 h of culture in the presence of delta 1-THC, indicating the irreversible nature of the blocking effect of delta 1-THC. By contrast, estradiol production following incubation of GC with testosterone (1 microgram/ml) was not inhibited by similar concentrations of delta 1-THC, thus suggesting that delta 1-THC does not inhibit aromatase activity in GC. In addition, delta 1-THC was shown to inhibit cAMP production as well as 125I-hCG binding capacity to GC. Administration of 8-Br-cAMP did not abolish the delta 1-THC-induced block, suggesting that the drug probably acts distal to the cAMP site of action.
在先前的研究中，已表明大麻的主要精神活性成分（δ1-四氢大麻酚）在动情前期下午早些时候给予正常发情周期的大鼠时，可抑制卵巢前列腺素的合成。这些结果提示该药物对卵巢有直接抑制作用。本研究的目的是评估δ1-四氢大麻酚对体外颗粒细胞（GC）类固醇生成的影响。将GC与δ1-四氢大麻酚（10 - 50微摩尔）一起孵育可有效抑制促黄体生成素刺激的孕激素产生。在δ1-四氢大麻酚存在下培养24小时后洗涤细胞，这种抑制作用并未消除，这表明δ1-四氢大麻酚的阻断作用具有不可逆性。相比之下，GC与睾酮（1微克/毫升）一起孵育后的雌二醇产生并未受到类似浓度的δ1-四氢大麻酚的抑制，因此表明δ1-四氢大麻酚不抑制GC中的芳香化酶活性。此外，已表明δ1-四氢大麻酚可抑制环磷酸腺苷（cAMP）的产生以及125I-人绒毛膜促性腺激素（hCG）与GC的结合能力。给予8-溴环磷酸腺苷并不能消除δ1-四氢大麻酚诱导的阻断作用，这表明该药物可能在cAMP作用位点的下游起作用。
