Exogenous
growth hormone has different actions depending on the method of administration. However, the effects of different modes of administration of the placental variant of
growth hormone on growth, body composition and
glucose metabolism have not been investigated. In this study, we examined the effect of pulsatile vs. continuous administration of recombinant variant of
growth hormone in a normal mouse model. Female C57BL/6J mice were randomized to receive vehicle or variant of
growth hormone (2 or 5 mg/kg per day) by daily
subcutaneous injection (pulsatile) or osmotic pump for 6 days. Pulsatile treatment with 2 and 5 mg/kg per day significantly increased
body weight. There was also an increase in liver, kidney and spleen weight via pulsatile treatment, whereas continuous treatment did not affect
body weight or organ size. Pulsatile treatment with 5 mg/kg per day significantly increased fasting plasma
insulin concentration, whereas with continuous treatment, fasting
insulin concentration was not significantly different from the vehicle-treated control. However, a dose-dependent increase in fasting
insulin concentration and decrease in
insulin sensitivity, as assessed by HOMA, was observed with both modes of treatment. At 5 mg/kg per day, hepatic
growth hormone receptor expression was increased compared to vehicle-treated animals, by both modes of administration. Pulsatile variant of
growth hormone did not alter the plasma
insulin-like growth factor-1 concentration, whereas a slight decrease was observed with continuous variant of
growth hormone treatment. Neither pulsatile nor continuous treatment affected hepatic
insulin-like growth factor-1
mRNA expression. Our findings suggest that pulsatile variant of
growth hormone treatment was more effective in stimulating growth but caused marked
hyperinsulinemia in mice.