Rapid Enzymatic Degradation

The effect of plasma on degradation of human growth hormonereleasing 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) ofGRH(144)-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(344)-NH2. Identity was also confirmed by co-elution of purified and synthetic peptides on HPLC. Biologic activity ofGRH(344)-NH2 was <10-3 that ofGRH(144)-NH2. After intravenous injection ofGRH(144)-NH2 in normal subjects, a plasma immunoreactive peak with HPLC retention comparable to GRH(344)-NH2 was detected within 1 min and the tl/2 of GRH(144)-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.