Williams C D, Horner A K, Catt K J
Endocr Res Commun. 1976;3(6):343-58. doi: 10.3109/07435807609073909.
The effects of 1-methyl 3-isobutyl xanthine (MIX) and theophylline on basal and gonadotropin-stimulated production of cyclic AMP and testosterone were evaluated in enzyme-dispersed testicular interstitial cells. The actions of these compounds upon precursor incorporation into RNA and protein were also examined in the same cell preparation. The considerable higher potency of MIX as a phosphodiesterase inhibitor was accompanied by a steeper dose-response curve for cyclic AMP recovery in incubation media of hormone-treated cells. Both inhibitors caused increases in basal and hormone-stimulated cyclic AMP levels. Although low concentrations of theophylline and MIX had no effect on the maximum levels of hCG-stimulated testosterone production, 10 mM theophylline and 1 mM MIX significantly inhibited steroidogenesis. Conversely, basal testosterone levels were increased by MIX and theophylline. The higher concentrations of MIX and theophylline also significantly inhibited precursor incorporation into RNA and protein. These actions of phosphodiesterase inhibitors upon RNA and protein synthesis could contribute to their inhibitory effects at high concentrations upon gonadotropin-induced steroidogenesis.
在酶分散的睾丸间质细胞中评估了1-甲基-3-异丁基黄嘌呤（MIX）和茶碱对基础及促性腺激素刺激的环磷酸腺苷（cAMP）生成和睾酮生成的影响。在相同的细胞制剂中还检测了这些化合物对前体掺入RNA和蛋白质的作用。MIX作为磷酸二酯酶抑制剂的效力明显更高，同时在激素处理细胞的孵育培养基中，cAMP恢复的剂量反应曲线更陡。两种抑制剂均使基础及激素刺激的cAMP水平升高。虽然低浓度的茶碱和MIX对人绒毛膜促性腺激素（hCG）刺激的睾酮生成的最大水平没有影响，但10 mM茶碱和1 mM MIX显著抑制类固醇生成。相反，MIX和茶碱使基础睾酮水平升高。较高浓度的MIX和茶碱也显著抑制前体掺入RNA和蛋白质。磷酸二酯酶抑制剂对RNA和蛋白质合成的这些作用可能导致它们在高浓度时对促性腺激素诱导的类固醇生成产生抑制作用。
