Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.
The effect of plasma on degradation of human growth hormone-releasing hormone (GRH) was examined in vitro and in vivo using high performance liquid chromatography (HPLC), radioimmunoassay (RIA), and bioassay. When GRH(1-44)-NH2 was incubated with human plasma, the t1/2 of total GRH immunoreactivity was 63 min (RIA). However, HPLC revealed a more rapid disappearance (t1/2, 17 min) of GRH(1-44)-NH2 that was associated with the appearance of a less hydrophobic but relatively stable peptide that was fully immunoreactive. Sequence analysis indicated its structure to be GRH(3-44)-NH2. Identity was also confirmed by co-elution of purified and synthetic peptides on HPLC. Biologic activity of GRH(3-44)-NH2 was less than 10(-3) that of GRH(1-44)-NH2. After intravenous injection of GRH(1-44)-NH2 in normal subjects, a plasma immunoreactive peak with HPLC retention comparable to GRH(3-44)-NH2 was detected within 1 min and the t1/2 of GRH(1-44)-NH2 (HPLC) was 6.8 min. The results provide evidence for GRH inactivation by a plasma dipeptidylaminopeptidase that could limit its effect on the pituitary.
D000328:Adult; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis / Q000097:blood* / Q000031:analogs & derivatives; D006207:Half-Life; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship
D000596:Amino Acids; D010446:Peptide Fragments; C040786:somatotropin releasing hormone (1-44)amide; D013007:Growth Hormone-Releasing Hormone