Cardiovascular, behavioural and metabolic consequences of growth hormone overexpression in transgenic mice

Abstract: Growth hormone (GH) exerts major effects on body growth and metabolism. GH is also important in controlling cardiovascular function and behaviour. To study the role of growth hormone in cardiovascular function and regulation of blood pressure, we overexpressed bovine growth hormone regulated by the metallothionein promoter in mice (Mt-bGH). This caused an increase in mean arterial pressure (MAP) which was not salt sensitive and was associated with an increased resistance of the hindquarter vasculature. No difference in the contractile strength of the mesenteric vascular wall or in endothelial function was observed. The Mt-bGH transgenic mice displayed more spontaneous locomotor activity than nontransgenic controls and had an enhanced capacity of brain 5-HT systems and an increased sensitivity to amphetamine. To study the influence of growth hormone action in the CNS on spontaneous locomotor activity and metabolism, we overexpressed bovine growth hormone specifically in the CNS (GFAP-bGH). This model showed that the enhanced spontaneous locomotor activity in Mt-bGH transgenic mice was not due to activation of GHR in the CNS but rather involves some peripheral factor(s). T3 and IGF-I are the two major candidates in enhanced spontaneous locomotor activity in Mt-bGH transgenic mice.At 18 weeks of age, the GFAP-bGH transgenic females were 31% heavier and males were 19% heavier than their littermate controls and also displayed an increased food intake. CT, MRI and organ dissections showed an increase of body fat in the GFAP-bGH transgenic mice. The serum leptin and insulin levels were increased while the glucose level was normal and the pancreas showed an islet hyperplasia in GFAP-bGH transgenic mice. Serum lipid analysis showed a decrease in TG and an increase in serum cholesterol. We observed a decrease in VLDL, an increase in LDL and a slight increase in HDL in GFAP-bGH transgenic mice. AGRP and NPY expression in the hypothalamus increased in GFAP-bGH transgenic mice. The increase in NPY was statistically significant in females only.