HUMAN GROWTH-HORMONE (HGH)-(44-191), A REPORTEDLY DIABETOGENIC FRAGMENT OF HGH, CIRCULATES IN HUMAN BLOOD - MEASUREMENT BY RADIOIMMUNOASSAY

The purpose of these experiments was to determine whether a 17-kilodal ton (K) fragment of human GH (hGH), hGH-(44-191), a peptide 10 times m ore potent than intact hGH in causing glucose intolerance in an animal model, circulates in human blood. Analysis of pituitary extracts and sera by Western blotting revealed the presence of a 17K hGH-immunoreac tive band in both samples. Monoclonal antibodies to recombinant hGH-(4 4-191) cross-reacted with the 17K hGH-immunoreactive band of the pitui tary. A RIA specific for hGH-(44-191) was developed using recombinant hGH-(44-191) as the tracer and standard, and a mouse anti-hGH-(44-191) serum as the source of antibody. The RIA detected hGH-(44-191) in hum an sera and pituitary extracts. The concentration of hGH-(44-191) in p ituitary glands was 1/100th to 1/500th of the hGH concentration, but i n serum its concentration averaged 1-2 times higher than that of hGH. Serum hGH-(44-191) concentrations were higher in pregnant than in nonp regnant women. The data document the existence of hGH-(44-191) in huma n pituitary gland and serum, and provide initial evidence that it may be physiologically produced. As its concentration is affected by the p hysiological state of the individual, it may play a role in the expres sion of the physiological and pathological actions of hGH.