The effect of N-acetylation of the corticotropin molecule on its extra-adrenal and adrenal actions has been evaluated by investigating the biological activities of several N-acetylated corticotropin related peptides and natural α-MSH. The N-acetylated peptides and α-MSH had a small but significant effect in stimulating both in vivo and in vitro adrenal steroidogenesis. These peptides exhibited a similarly weak lipid mobilizing action as measured by the in vitro release of free fatty acids from rat epididymal adipose tissue. In contrast to the hypoglycemic activity of corticotropin, the Nacetylated peptides resulted in significant hyperglycemia when they were administered to mice. This hyperglycemia occurred in adrenalectomized animals and could be demonstrated with α- MSH, but not β-MSH. The hyperglycemia was not due to an antagonism of the peripheral action of insulin and it occurred in spite of a direct action of the N-acetylated peptides in stimulating insulin secretion. The hyperglycemia was associated with a decrease in liver glycogen, and therefore was the result of an increase in hepatic glucose output. Thus, N-acetylation of the ACTH molecule appears to create a new metabolic action rather than just quantitatively changing its spectrum of established actions.(Endocrinology79: 635, 1966)
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Lebovitz et al. (1966) studied this question.