Novel variants of adrenocorticotrophic hormone in porcine anterior pituitary.
Extracts of porcine anterior pituitary contain several corticotrophic variants of ACTH 1-39. They were isolated by adsorption chromatography, ion-exchange chromatography and reverse-phase high-performance liquid chromatography. Four variants were then identified as starting and ending at positions corresponding to ACTH 1-38, 1-37, 7-39 and 7-38. Several of these fragments were recovered in chromatographically multiple forms. Although all fragments isolated had corticotrophic activity (measured on isolated rat adrenal cells) those with a shortened N-terminal region had a lower potency than those with an intact N-terminal region. Corticotrophic activity of porcine ACTH 7-38 was detected in a preparation with a beta-aspartyl shift at position 25. However, in agreement with previous studies, synthetic human ACTH 7-38, in which an intact Asn-Gly bond was structurally proven, possessed no such activity. The results indicate that position 25 as well as positions 1-6 are important for corticotrophic activity, and that a deamidative beta-aspartyl shift at position 25 can influence the activity.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000096:biosynthesis; D010446:Peptide Fragments / Q000302:isolation & purification; D010903:Pituitary Gland, Anterior / Q000032:analysis*; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine
C027550:ACTH (1-38); D010446:Peptide Fragments; C026034:ACTH (7-38); C042876:ACTH (1-37); D000324:Adrenocorticotropic Hormone; C042875:ACTH (7-39); D003345:Corticosterone