The actions of N-terminal fragments of corticotrophin on steroidogenesis in dispersed rat adrenal cells in vitro.
The finding that the rat adrenal zona glomerulosa cell shows specific sensitivity to stimulation by alpha-MSH and related peptides has been confirmed both in vivo and in vitro, raising the possibility that alpha-MSH may have a physiological role in the control of glomerulosa function and aldosterone secretion. To define more closely the structural features which confer teh specificity of the glomerulosa response, other ACTH derived peptides have been tested for their specificity of actions on rat adrenal cells in vitro. The peptides tested were ACTH(5-24), ACTH(1-12), ACTH(1-14), ACTH(1-15), ACTH(1-16) and ACTH(1-17). Their actions were compared with those of alpha-MSH and ACTH(1-24). All of the ACTH-derived peptides stimulated glomerulosa corticosterone production with sensitivities similar to that of alpha-MSH; minimum effective concentration was 10 nmol/l. Also, like alpha-MSH, the shorter ACTH peptides stimulated aldosterone production only relatively weakly in these cells from animals on normal sodium intake. Only ACTH(5-24), ACTH(1-16) and ACTH(1-17) stimulated fasciculata/reticularis cells at concentrations up to 1 mumol/1. The actions of all of the shorter peptides were thus unlike those of ACTH(1-24) which stimulates both cell types with approximately equal sensitivity, and which furthermore strongly stimulates aldosterone production. The data suggest that the 18-24 region of the ACTH molecule contains the signal for a fasciculata/reticularis response, and the region 1-13 that for glomerulosa specificity. They confirm the view that, in the rat, alpha-MSH itself may be the specific pituitary glomerulosa-stimulating agent which much experimental work has predicted. They also indicate that synthetic ACTH(1-17) analogues should be used with caution.
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D003345:Corticosterone