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The hypoglycaemic response to human growth hormone and its synthetic 4-15 fragment were studied in 16-18 day-old and 45-50 day-old normal male rats using three different bioassay system: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptor of hepatic plasma membranes, and (3) activation of insulin-dependent glycogen synthase in muscle. The mean level of the endogenous growth hormone in the 16-18 day-old group was 11 +/- 4 ng/ml and that of the 45-50 day-old group was 164 +/- 35 ng/ml. A hypoglycaemic action of human growth hormone was observed in the baby animals but not in the adults. The synthetic 4-15 fragment was found, at a similar dose to that of the intact molecule, to enhance hypoglycaemia in both groups of rats. In exact parallel, growth hormone increased hepatic insulin binding and activated muscle glycogen synthase only in baby rats but the synthetic 4-15 fragment affected both baby and adult animals in the same way. The molecular mechanism for the diminution of the responses to the intact molecule of growth hormone in normal adult rats remains to be identified. However, the present studies provide the first evidence on the hypoglycaemic response to growth hormone in vivo in normal rats without any previous chemical or surgical treatment.

Comparison of hypoglycaemic responses to human growth hormone and the synthetic 4?15 fragment between 16?18 day-old and 45?50 day-old rats