On the mechanism of action of the adrenocorticotrophic hormone. The stimulation of the activity of enzymes involved in pregnenolone synthesis.

摘要: Abstract Rat adrenal steroidogenesis has been measured in a system consisting of mitochondria, microsomes, succinate, Mg++, TPNH, DPN+, and phosphate. With incubations at 20°, the rate corticosterone formation found to be biphasic with rapid primary lasting for about 4 6 min, followed by slower secondary which continues least another 15 min. Of two subcellular fractions, mitochondrial fraction is rate-limiting one. Administration adrenocorticotrophic hormone (ACTH) min before killing experimental animals resulted 2- 3-fold increase synthesis. The was due changes occurred only mitochondria; microsomes from ACTH-treated control were identical their activity. direct assay reactions involved synthesis, that is, synthesis pregnenolone, conversion pregnenolone progesterone, transformation progesterone deoxycorticosterone, 11-hydroxylation deoxycorticosterone showed mitochondria increased ACTH. In addition, slowest reaction, even after ACTH stimulation. Mitochondria "pretreated" exposure water inclusion Ca++ incubation medium. Pretreated both rats greater rates than corresponding intact mitochondria. Prior administration cycloheximide eliminates ACTH-induced However, if are pretreated, then no effect on activity, activity equal other studied, 11-hydroxylation, not affected. These data indicate stimulation does involve an amount enzyme directly participates but such enzyme. Adrenal more sensitive swelling agents animals. hypothesis controls determining efflux hence extent feedback inhibition its own consistent obtained.