KINETIC ASPECTS OF CYCLOHEXIMIDE-INDUCED REVERSAL OF ADRENOCORTICOTROPIN EFFECTS ON STEROIDOGENESIS AND ADRENAL PHOSPHOLIPIDS INVIVO
KINETIC ASPECTS OF CYCLOHEXIMIDE-INDUCED REVERSAL OF ADRENOCORTICOTROPIN EFFECTS ON STEROIDOGENESIS AND ADRENAL PHOSPHOLIPIDS INVIVO
复制标题
DOI：
10.1073/pnas.77.12.7189
复制
发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
LARSON, RE
中科院分区：
文献类型：
--
作者：
FARESE, RV;SABIR, MA;LARSON, RE
IP地址。注射最大有效剂量的ACTH(1-24分钟)可引起大鼠肾上腺磷脂的最大升高，分别为1.5-2分钟内的磷脂酸，4-6分钟内的磷脂酰肌醇和磷脂酰甘油，5-15分钟内的磷脂酰肌醇和皮质酮。ACTH(1-18)持续的最大肾上腺刺激导致肾上腺磷脂酸、磷脂酰肌醇、磷脂酰甘油、多磷肌醇和皮质酮持续增加。在这种稳定状态下，用放线菌素治疗会导致所有这些物质迅速下降到基础水平。肾上腺磷脂酸、磷脂酰肌醇、聚磷脂酰肌醇、磷脂酰甘油和皮质酮在放线菌酮抑制作用下的半衰期分别为0.15、1.0、1.7、3.3和3.5min。计算的ACTH最大刺激时的产生率分别为每分钟1060、991、90、34和41nmol/g组织。显然，ACTH对磷脂酸从头合成的初始作用可以解释后来观察到的CDP-二酰甘油其他磷脂衍生物的增加，ACTH诱导的磷脂酸的增加需要一种不稳定的蛋白质。多磷肌醇-聚甘油磷脂途径对激素刺激反应迅速，类固醇合成的变化与这一磷脂途径的变化密切相关，并且这一途径的刺激是快速可逆的。
I.p. injection of maximally effective doses of ACTH(1-24) provoked maximal increases in rat adrenal phospholipids as follows: phosphatidic acid within 1.5-2 min, phosphatidylinositol and phosphatidylglycerol within 4-6 min and polyphosphoinositides and corticosterone within 5-15 min. Continued maximal adrenal stimulation by ACTH(1-18) treatment caused sustained increases in adrenal phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, polyphosphoinositides and corticosterone. Treatment with cycloheximide during this steady-state caused rapid decreases in all of these substances to basal levels. The observed half-lives of adrenal phosphatidic acid, phosphatidylinositol, polyphosphoinositides, phosphatidylglycerol, and corticosterone during cycloheximide inhibition were 0.15, 1.0, 1.7, 3.3 and 3.5 min, respectively. Calculated production rates during maximal ACTH stimulation were 1060, 991, 90, 34 and 41 nmol/g of tissue per min, respectively. Apparently an initial effect of ACTH on de novo synthesis of phosphatidic acid can account for all subsequently observed increases in other phospholipid derivatives of CDP-diacylglycerol, a labile protein is required for the ACTH-induced increase in phosphatidic acid, the phosphatidate .fwdarw. polyphosphoinositide-polyglycerophospholipid pathway is rapidly and dramatically responsive to hormonal stimulation, changes in steroidogenesis correlate well with changes in this phospholipid pathway and stimulation of this pathway is rapidly reversible.