Feuilloley M, Netchitaïlo P, Delarue C, Leboulenger F, Benyamina M, Vaudry H
Groupe de Recherche en Endocrinologie Moléculaire, UA CNRS 650, Unité allieée à l'INSERM, Faculté des Sciences, Université de Rouen, Mont-Saint-Aignan, France.
Pathol Biol (Paris). 1987 Oct;35(8):1173-7.
In order to determine the role of the microtubular network in adrenal steroidogenesis, we have studied the effect of vinblastine, a potent antimicrotubular agent on corticosteroid secretion by frog adrenocortical fragments in perifusion. Administration of vinblastine (10(-5) M) did not alter the spontaneous secretion of corticosteroids and had no effect on the steroidogenic response to angiotensin II and prostaglandin E1. In contrast, vinblastine induced a marked decrease in ACTH-induced stimulation of corticosteroidogenesis. To investigate further the site of action of the microtubular system in ACTH-induced steroidogenesis we have studied the effect of vinblastine on the different steps of the stimulation of the adenylate cyclase system. Our results show that vinblastine does not alter the stimulatory action of cAMP, the second messenger of ACTH. In addition, the corticosteroidogenic effect of forskolin and NaF (which respectively stimulate the adenylate-cyclase subunit and the guanyl nucleotide regularly protein) was not affected by vinblastine. These results indicate that the microtubular network interferes in the coupling of the secretory response of the adrenal glands to ACTH, either at the level of the binding of ACTH to its receptor or in the coupling of the receptor to the guanyl nucleotide regulatory protein.
为了确定微管网络在肾上腺类固醇生成中的作用,我们研究了长春碱(一种有效的抗微管剂)对灌注中青蛙肾上腺皮质碎片皮质类固醇分泌的影响。给予长春碱(10⁻⁵ M)并未改变皮质类固醇的自发分泌,且对血管紧张素II和前列腺素E1的类固醇生成反应没有影响。相反,长春碱显著降低了促肾上腺皮质激素(ACTH)诱导的类固醇生成刺激。为了进一步研究微管系统在ACTH诱导的类固醇生成中的作用位点,我们研究了长春碱对腺苷酸环化酶系统刺激不同步骤的影响。我们的结果表明,长春碱不会改变ACTH的第二信使环磷酸腺苷(cAMP)的刺激作用。此外,福斯可林和氟化钠(分别刺激腺苷酸环化酶亚基和鸟苷酸调节蛋白)的皮质类固醇生成作用不受长春碱影响。这些结果表明,微管网络在ACTH与受体结合水平或受体与鸟苷酸调节蛋白的偶联水平上干扰了肾上腺对ACTH分泌反应的偶联。