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-kilodalton (K) fragment of human GH (hGH), hGH-(44-191), a peptide 10 times more 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-immunoreactive band in both samples. Monoclonal antibodies to recombinant hGH-(44-191) cross-reacted with the 17K hGH-immunoreactive band of the pituitary. 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 human sera and pituitary extracts. The concentration of hGH-(44-191) in pituitary glands was 1/100th to 1/500th of the hGH concentration, but in serum its concentration averaged 1-2 times higher than that of hGH. Serum hGH-(44-191) concentrations were higher in pregnant than in nonpregnant women. The data document the existence of hGH-(44-191) in human pituitary gland and serum, and provide initial evidence that it may be physiologically produced. As its concentration is affected by the physiological state of the individual, it may play a role in the expression of the physiological and pathological actions of hGH.