Adrenocortical response to corticotropin is potentiated by part of the amino-terminal region of pro-corticotropin/endorphin.
Five peptides derived from pro-corticotropin/endorphin (pro-ACTH/endorphin), the pituitary corticotroph cell prohormone, were bioassayed with isolated rat adrenocortical cells: alpha- and beta-melanotropin, beta-lipotropin, beta-endorphin, and the amino-terminal region of pro-ACTH/endorphin known as "16k fragment." The effect of each on steroidogenesis was measured at potentially physiological concentrations (0.01-1 nM) in both the absence and presence of varying concentrations of ACTH-(1-24). Of the peptides tested, only 16k fragment, the amino-terminal region of pro-ACTH/endorphin, has a slight but significant potentiating effect on ACTH-(1-24) action. Prior treatment of 16k fragment with trypsin for 30 sec dramatically increases this dose-dependent synergism. Experiments performed in vivo with hypophysectomized female rats indicate that the trypsin digest of 16k fragment stimulates cholesterol ester hydrolase (cholesterol esterase; sterol-ester acylhydrolase, EC 3.1.1.13) activity in the adrenal cortex but fails to activate cholesterol side-chain cleavage. The effect of the trypsinized material can therefore be qualitatively distinguished from that of ACTH-(1-24). When both ACTH-(1-24) and the digest are administered together, a synergistic increase in serum corticosterone concentration results. We propose that a portion of 16k fragment molecule may play a hormonal role in the control of adrenocortical steroidogenesis.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000096:biosynthesis; D004723:Endorphins / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D002787:Sterol Esterase / Q000096:biosynthesis
D004723:Endorphins; D010446:Peptide Fragments; D011498:Protein Precursors; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D002787:Sterol Esterase; D003345:Corticosterone