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The Acute Effects of Growth Hormone on Amino Acid Transport and Protein Synthesis Are Due to Its Insulin-Like Action^*

C.M. CAMERON, J.L. KOSTYO, N.A. ADAMAFIO, P. BROSTEDT, P. ROOS, A. SKOTTNER, A. FORSMAN, L. FRYKLUND and B. SKOOG

Department of Physiology, University of Michigan Medical School (C.M.C., J.L.K., N.A.A.) Ann Arbor, Michigan 48109-0622
the Department of Biochemistry, University of Uppsala (P.B., P.R.) Uppsala
KabiVitrium AB (A.S., A.F., L.F., B.S.) Stockholm, Sweden

Address requests for reprints to: Dr. Jack L. Kostyo, Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622.

Abstract

GH has acute stimulatory effects on amino acid transport and protein synthesis in a variety of tissues, but it has not been established whether these effects are expressions of the growth-promoting property of GH or of its separate insulin-like action. The 20,000-dalton structural variant of human GH (20K hGH) has been shown to have a high ratio of growth-promoting to insulin-like activity compared to native hGH (22K hGH), suggesting that it could be used as a tool to address the above question. Therefore, experiments were conducted to compare the relative abilities of native 22K hGH and 20K hGH, when added in vitro, to stimulate amino acid transport and protein synthesis in the isolated diaphragm of the female hypophysectomized rat. Paired intact hemidiaphragms were preincubated for 1 h in the absence or presence of various concentrations of 22K or 20K hGH. Then, 3-O-[¹⁴C]methylglucose was added to the medium to measure sugar transport as a test of insulin-like activity, and either -[³H]aminoisobutyric acid acid or [³H] phenylalanine was also added to measure amino acid transport or protein synthesis, respectively, during a final hour of incubation. When the responses to the various concentrations of 22K and 20K were compared, 20K hGH was only about 20% as effective as 22K in stimulating 3-O-methylglucose transport, reflecting its markedly attenuated insulin-like activity on the diaphragm. Similarly, 20K hGH was only 20% as effective as 22K hGH in stimulating -aminoisobutyric acid transport and phenylalanine incorporation into protein in the same muscles. Therefore, these findings support the idea that the rapid stimulatory effects of GH on amino acid transport and protein synthesis are expressions of the insulin-like action of GH and are not components of the response of target cells to its growthpromoting action. (Endocrinology 122: 471–474,1988)

Footnotes

^* Presented in part at the 69th Annual Meeting of The Endocrine Society, June 1987, Indianapolis, IN. This work was supported by the Swedish Medical Council (Project 5921).

Recipient of National Research Service Award AM-07268.

Recipient of a fellowship from the American Diabetes Association — Michigan Affiliate.

Received July 22, 1987.

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