Effects of ovine corticotropin-releasing hormone and FK 33-824 (met-enkephalin analogue) on the secretions of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in patients with Addison's disease.
The responses of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH) and IR-ACTH levels to ovine corticotropin-releasing hormone (CRF) and FK 33-824 (Met-Enkephalin analogue) were studied in nine patients with Addison's disease. The basal plasma levels (mean +/- SE) of IR-Nt, IR-Ep, IR-LPH and IR-ACTH were significantly higher in patients with Addison's disease (4459 +/- 975 pg/ml, 132 +/- 25 pg/ml, 4425 +/- 1030 pg/ml, 553 +/- 89 pg/ml, respectively) than in the normal controls (202 +/- 38 pg/ml, 7 +/- 2 pg/ml, 101 +/- 18 pfi/ml, 53 +/- 16 pg/ml, respectively). Ovine CRF produced rapid and concomitant increases in plasma levels of IR-Nt, IR-Ep, IR-LPH and IR-ACTH. Ep and ACTH levels reached a peak at 30 min. On the other hand, Nt and LPH levels reached a peak at 60 min and these levels gradually decreased up to 120 min. The molar concentrations of these IR-peptides in plasma were changed in close parallel fashion to one another. FK 33-824 produced a pronounced and concomitant fall in IR-Nt, IR-EP, IR-LPH, and IR-ACTH levels. These results support the theory that Nt, Ep, LPH and ACTH are produced simultaneously from POMC as a common precursor in the pituitary gland and are secreted concomitantly under various conditions such as stimulation by CRF and inhibition by FK 33-824 in patients with Addison's disease.
D000224:Addison Disease / Q000188:drug therapy* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000627:therapeutic use*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000627:therapeutic use*; D004723:Endorphins / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000378:metabolism
D004723:Endorphins; D010446:Peptide Fragments; D001615:beta-Endorphin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008083:beta-Lipotropin; D006854:Hydrocortisone