Steroidogenic activity of fragments of adrenocorticotropin with arginine in residue positions 3 and 5.
The maximal steroidogenic response (Smax) to adrenocorticotropin (ACTH) is enhanced by the substitution of arginine in position 3. Though the Smax of adrenocorticotropin-(3-10)-octapeptide [ACTH-(3-10)] is only 20% of ACTH-(1-24) in isolated rabbit adrenal cells and 10% in rat cells, [Arg3]ACTH-(3-10) has an Smax comparable to that of the longer peptide. Activity determined from the midpoints of dose-response curves (A50), however, is several orders of magnitude less. The Smax of ACTH-(4-10) is not significantly different from that of the 3-10 analog. Substitution of arginine in the 5 position of ACTH-(4-10) decreases activity for rabbit cells, but does not affect activity for rat cells. The substitution of arginine in the 5 position of ACTH-(1-20) markedly decreases Smax in rabbit but not rat cells. The Smax of [Arg 3,5)]ACTH-(3-10), containing both substitutions, is greater than that of ACTH-(3-10), but much less than that of [Arg3]acth-(3-10) in both species studied. These findings contrast with those in the rabbit adipocyte, where both arginine-containing ACTH analogs have enhanced activity and the effects of both substitutions in a single peptide are additive.
D000273:Adipose Tissue / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D000305:Adrenal Cortex Hormones; D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D001120:Arginine