Asem E K, Hertelendy F
Gen Comp Endocrinol. 1986 Oct;64(1):107-11. doi: 10.1016/0016-6480(86)90035-3.
Unstimulated (basal) as well as luteinizing hormone (LH)-promoted progesterone production in collagenase-dispersed hen granulosa cells was inhibited in a dose-related manner by two phenothiazines, trifluoperazine (TFP) and chlorpromazine (CP), both of which are known calmodulin antagonists. Using TFP, the more potent antagonist of the two, it was found that LH-stimulated cyclic AMP production was also suppressed. Moreover, TFP attenuated the steroidogenic effects of both 8-bromo-cyclic AMP and isobutylmethylxanthine but had no effect on the conversion of pregnenolone to progesterone. The inhibitory effects of TFP on steroidogenesis were reversible. It is concluded that phenothiazines inhibit steroidogenesis in ovarian granulosa cells by acting at multiple sites both proximal and distal to cyclic AMP generation without influencing the enzyme complex responsible for the conversion of pregnenolone to progesterone. The results are discussed in relation to calmodulin- and non-calmodulin-mediated actions of phenothiazines.
两种吩噻嗪类药物三氟拉嗪（TFP）和氯丙嗪（CP）（二者均为已知的钙调蛋白拮抗剂）以剂量相关的方式抑制了胶原酶分散的母鸡颗粒细胞中未受刺激（基础状态）以及促黄体生成素（LH）促进的孕酮生成。使用两种拮抗剂中活性更强的TFP发现，LH刺激的环磷酸腺苷（cAMP）生成也受到抑制。此外，TFP减弱了8-溴环磷酸腺苷和异丁基甲基黄嘌呤的类固醇生成作用，但对孕烯醇酮向孕酮的转化没有影响。TFP对类固醇生成的抑制作用是可逆的。得出的结论是，吩噻嗪类药物通过作用于环磷酸腺苷生成近端和远端的多个位点来抑制卵巢颗粒细胞中的类固醇生成，而不影响负责孕烯醇酮向孕酮转化的酶复合物。结合吩噻嗪类药物的钙调蛋白介导和非钙调蛋白介导的作用对结果进行了讨论。
