Human plasma proopiomelanocortin N-terminal peptide and adrenocorticotropin: circadian rhythm, dexamethasone suppression, and corticotropin-releasing hormone stimulation.

The circadian rhythm, suppression with dexamethasone, and stimulation by corticotropin-releasing hormone (CRH) of plasma immunoreactive (IR) proopiomelanocortin N-terminal (NT) and IR-ACTH were studied in nine normal subjects and two patients with Addison's disease. The RIA for human NT (hNT) used was specific for NT except for partial cross-reactivity with gamma 2MSH. In normal subjects, plasma IR-hNT and IR-ACTH had almost parallel circadian rhythms and were suppressed by dexamethasone. The mean plasma levels of IR-hNT and IR-ACTH at 0800 h were 140 +/- 23 (SD) and 23 +/- 5 pg/ml, respectively. Plasma IR-hNT increased in parallel with IR-ACTH 15 to 30 min after iv injection of 100 micrograms ovine CRH. Maximum percent increases in plasma IR-hNT and IR-ACTH were 185 +/- 47 and 235 +/- 10%, respectively. In Addison's disease, on the other hand, plasma levels of IR-hNT and IR-ACTH were markedly elevated and the circadian rhythms were parallel. The mean plasma IR-hNT and IR-ACTH levels at 0900 h were 4363 and 1750 pg/ml, respectively. These results suggest that plasma hNT and ACTH are produced from a common precursor in the pituitary gland and secreted concomitantly under various physiological conditions such as stimulation by CRH and inhibition by glucocorticoid.