Stress-Induced Secretion of Human Growth Hormone in Transgenic Mice

Abstract

Abstract

The effect of stress on human growth hormone (hGH) secretion was studied in transgenic mice. Experiments were conducted on fourth, fifth, and sixth generation male mice carrying a fusion gene, consisting of the promoter sequence of the mouse metallothionein I gene ligated to the hGH structural gene (mMT-I/hGH). In animals adapted to a controlled photoperiod, basal (unstimulated) levels of plasma hGH exhibited a diurnal cycling, with peak values occurring during the later half of the light period (15.5 ± 1.0 vs 10.7 ± 0.9 ng/ml, mean ± SE, light versus dark, respectively). Food deprivation (5 days) led to elevated levels of plasma hGH (11.0 ± 0.7 vs 32.0 ± 4.2 ng/ml, preversus post-fast, respectively) accompanied by weight loss (49.5 ± 0.8 vs 34.3 ± 0.7 g), and hypoglycemia (7.8 ± 0.2 vs 5.0 ± 0.3 mM); glucose administration (5% drinking solution ad libitum) blocked the changes in levels of plasma hGH (12.2 ± 1.1 vs 13.8 ± 0.8 ng/ml) and plasma glucose (7.4 ± 0.3 vs 7.9 ± 0.5 mM), although the animals still sustained significant weight loss (44.9 ± 1.6 vs 35.2 ± 1.1 g). Vigorous exercise (swimming, 4 hr) produced a small but significant increase in plasma hGH, 12.1 ± 1.1 ng/ml (1 hr pre-swim) vs 16.7 ± 0.6 ng/ml (immediately post-swim). These findings indicate that the mMT-I/hGH transgene is responsive to the physiologic status of the host animal. Taken together with information regarding the heterologous components of the fusion gene, these data are consistent with the view that the hGH (structural) sequence may play a role in the response to stress.