Carnegie J A, Tsang B K
Biol Reprod. 1984 Mar;30(2):515-22. doi: 10.1095/biolreprod30.2.515.
The involvement of the calcium-calmodulin system in the gonadotropic regulation of granulosa cell steroidogenesis during follicular development was assessed by comparing the effects of agents known to alter calcium metabolism or calmodulin activity on gonadotropin-stimulated progesterone production by rat granulosa cells at different stages of cellular differentiation. Granulosa cells from pregnant mare's serum gonadotropin-injected rats (PMSG-cells) could be stimulated to produce steroids by both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), whereas those from 17 beta-estradiol-pretreated animals (E2-cells) only responded to to FSH. Although PMSG-cells demonstrated greater capacities for adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and progesterone production, their sensitivity to the various agents tested was similar to that of the E2-cells. [Ethylene-bis(oxyethylene-nitrilo)] tetraacetic acid (EGTA) markedly reduced both basal and FSH-stimulated progesterone production by both cell preparations. Verapamil, an agent which inhibits cellular uptake of calcium, attenuated cyclic AMP and progesterone production by both cell groups at similar concentrations. Calcium ionophore A23187, a stimulator of cellular calcium uptake, significantly stimulated progesterone production by both E2-cells and PMSG-cells. While FSH-stimulated progesterone production by both cell groups was lowered by the calmodulin inhibitor, 1-[bis(p-chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4-dichlorobenzy loxy) phenethyl] imidazolium chloride (R24571), cyclic AMP production by PMSG-cells in response to both FSH and LH was significantly reduced by R24571 and trifluoperazine (TFP), another calmodulin inhibitor. These findings indicate that the calcium-calmodulin system is involved in the regulation of granulosa cell steroidogenesis by both FSH and LH. Its participation in the gonadotropic regulation is independent of the stage of follicular maturation and cellular differentiation.
通过比较已知可改变钙代谢或钙调蛋白活性的试剂对不同细胞分化阶段大鼠颗粒细胞促性腺激素刺激的孕酮产生的影响，评估钙 - 钙调蛋白系统在卵泡发育过程中对颗粒细胞类固醇生成的促性腺调节中的作用。来自注射孕马血清促性腺激素的大鼠的颗粒细胞（PMSG细胞）可被促卵泡激素（FSH）和黄体生成素（LH）刺激产生类固醇，而来自17β - 雌二醇预处理动物的颗粒细胞（E2细胞）仅对FSH有反应。尽管PMSG细胞显示出更高的腺苷3':5'-环磷酸（环AMP）和孕酮产生能力，但其对所测试的各种试剂的敏感性与E2细胞相似。[乙二胺双（氧乙基腈）]四乙酸（EGTA）显著降低了两种细胞制剂的基础和FSH刺激的孕酮产生。维拉帕米是一种抑制细胞摄取钙的试剂，在相似浓度下减弱了两个细胞组的环AMP和孕酮产生。钙离子载体A23187是一种细胞摄取钙的刺激剂，显著刺激了E2细胞和PMSG细胞的孕酮产生。虽然钙调蛋白抑制剂1 - [双（对氯苯基）甲基] - 3 - [2,4 - 二氯 - β - （2,4 - 二氯苄氧基）苯乙基]咪唑氯化物（R24571）降低了两个细胞组FSH刺激的孕酮产生，但R24571和另一种钙调蛋白抑制剂三氟拉嗪（TFP）显著降低了PMSG细胞对FSH和LH反应的环AMP产生。这些发现表明钙 - 钙调蛋白系统参与了FSH和LH对颗粒细胞类固醇生成的调节。其在促性腺调节中的参与与卵泡成熟和细胞分化阶段无关。
