Effect of (1-24)adrenocorticotrophin stimulation on the rate of corticosterone synthesis by the rat adrenal cortex.
The rate of corticosterone synthesis by the rat adrenal gland was measured in vitro, using a cell-free system, following the in vivo administration of (1-24)ACTH. The doses of ACTH used were 50, 100 and 250 micrograms ACTH/kg body weight. With all 3 doses of ACTH there was a significant increase in the rate of corticosterone synthesis within the first 5 min; this initial increase in rate did not vary with the dose of ACTH given. With both the 50 and 100 micrograms/kg doses the new rate of synthesis was maintained without further change, up to 30 min post-injection. In the case of the 250 micrograms/kg dose there was a second significant increase in the rate of corticosterone synthesis observed after 20 min. The results are discussed in the light of the hypothesis that the differential response of the adrenal gland represents the binding of ACTH to two receptors; a high affinity receptor of low abundance and a low affinity receptor of greater abundance. The results are consistent with the initial steroidogenic response resulting from binding to the high affinity receptors. Because of their low abundance these receptors may be completely occupied even at low doses of ACTH, thus explaining the dose-independent nature of the initial response to ACTH. Binding to the more abundant low affinity receptors may be associated with the secondary dose-dependent enhanced synthesis rate, a response which may be mediated via c-AMP.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002474:Cell-Free System; D003345:Corticosterone / Q000378:metabolism*; D003366:Cosyntropin / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats
D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone