Mechanism of ACTH action : Intracellular flux of cholesterol during ACTH-induced corticoidogenesis

• Published in: Japanese journal of pharmacology 1983, Vol.33, p.131-131
• Main Authors: Ohno, Yuji, Sekimoto, Takehito, Uzawa, Shun-ichi, Tsurui, Masashi, Yonezawa, Yoshiko, Imagawa, Nobuyuki, Yanagibashi, Kazutoshi, Matsuba, Michio
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)60395-1

Corticoidogenic response to ACTH in the adrenal cortex is strictly controlled by the rate of cholesterol bound to cyt.P450scc which is located in the inner mitochondrial membrane. Thus, the rate of the intracellular movement of cholesterol induced by ACTH was investigated in bovine adrenocortical cells. Cholesterol and pregnenolone were measured by enzymatic assay and Cortisol by the fluorometrical assay. (1) In the presence of 1 nM ACTH, the amount of the intracellular free cholesterol was not affected, whereas about 0.3 nmoles of the cholesterol esters per 10^ cells decreased in 60 min incubation. Most of the diminished cholesterol esters in the cells were thought to be utilized as a substrate of steroidogenesis. (2) The rate_of pregnenolone formation induced by 1 nM ACTH was about 0.3 nmoles/105 cells/hr, which was just the same as that of Cortisol production for 60 min incubation. There was a stoichiometrical correlation between the decrement of the intracellular cholesterol esters and the increment of either pregnenolone or Cortisol formation in the cells. It is therefore concluded that the intracellular cholesterol esters might be the sole substrate in the corticoidogenic response to ACTH in the adrenal cortex. Thus, ACTH could activate cholesterol ester hydrolase in adrenocortical cells to facilitate the transport of the free cholesterol to the inner mitochondrial membrane, and the translocated cholesterol in the inner membrane rapidly interacts with cyt.P450scc to convert to pregnenolone and other corticoids.