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Research Article Free access | 10.1172/JCI107491

Metabolic Effects of Plasmin Digests of Human Growth Hormone in the Rat and Man

John B. Mills, Charles R. Reagan, Daniel Rudman, Jack L. Kostyo, P. Zachariah, and Alfred E. Wilhelmi

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Mills, J. in: PubMed | Google Scholar

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Reagan, C. in: PubMed | Google Scholar

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Rudman, D. in: PubMed | Google Scholar

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Kostyo, J. in: PubMed | Google Scholar

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Zachariah, P. in: PubMed | Google Scholar

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322

Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

Find articles by Wilhelmi, A. in: PubMed | Google Scholar

Published November 1, 1973 - More info

Published in Volume 52, Issue 11 on November 1, 1973
J Clin Invest. 1973;52(11):2941–2951. https://doi.org/10.1172/JCI107491.
© 1973 The American Society for Clinical Investigation
Published November 1, 1973 - Version history
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Abstract

As a first step in our study of structure-function relationships among primate and non-primate growth hormones, human growth hormone (hGH) was subjected to the limited digestive activity of human plasmin. The lyophilized whole digest, containing less than 2% of unchanged hormone, had an average of 2.3 new amino-terminal groups per mole. The digest had the same potency as the native hormone (a) in causing weight gain in hypophysectomized rats; (b) in stimulating somatomedin production in hypophysectomized rats; (c) in stimulating upake of [3H]leucine into isolated diaphragm of hypophysectomized rats; (d) in accelerating transport of [14C]α-aminoisobutyric acid into isolated diaphragm of hypophysectomized rats; (e) in stimulating uptake of [3-0-methyl-14C]glucose by isolated adipose tissue of hypophysectomized rats; (f) in accelerating conversion of [14C]glucose to 14CO2 by isolated epididymal adipose tissue of hypophysectomized rats. The digest also caused glucosuria in partially pancreatectomized rats treated with dexamethasone.

These metabolic actions of plasmin-digested hGH in the array of animal tests were confirmed by comparable effects elicited in 11 human subjects (nine pituitary-deficient children and adolescents and two nondeficient adults). A single injection of the plasmin digest caused an increase in plasma free fatty acids and a fall in plasma amino acids. Seven daily injections caused positive balances of nitrogen, phosphorous, sodium, and potassium, gain in body weight, and in two of three subjects impairment of glucose tolerance. The potency of the plasmin digest in producing these metabolic effects in man was comparable to that of native hGH.

Thus, 2-3 bonds in the hGH molecule can be cleaved by plasmin without impairing the hormone's growthpromoting, anabolic, diabetogenic, and adipokinetic actions for rat and man.

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