Growth hormone effects on hepatic glutamate handling in vivo

Growth hormone administration affects growth in hypophysectomized animals by depressing urea synthesis and redistributing nitrogen into protein. Because the liver is the site of ureagenesis and glutamine is the major interorgan nitrogen vehicle, we studied hepatic glutamine uptake in relation to urea release in hypophysectomized and growth hormone-supplemented, 100 micrograms/100 g body wt hypophysectomized rats. In vivo hepatic balances for glutamine, glutamate, alanine, and urea were performed on anesthetized animals by simultaneous measurement of flow through the liver and the respective arteriovenous and portovenous concentration differences. On the whole animal level, growth hormone-administered hypophysectomized rats exhibited restored growth and decreased urea excretion associated with a reduction in arterial urea and elevation in arterial glutamate, but glutamine and alanine concentrations were unchanged. On the organ level, growth hormone treatment reduced hepatic urea release from 3,145 +/- 432 to 1,954 +/- 320 nmol.min-1.100 g-1. However, neither glutamine uptake, 342 +/- 110 and 494 +/- 135 nmol.min-1.100 g-1 nor alanine uptake, 522 +/- 120 vs. 363 +/- 109 nmol.min-1.100 g-1 were altered by growth hormone treatment. In marked contrast, net glutamate uptake by the hypophysectomized rat liver, 71 +/- 15 nmol.min-1.100 g-1, was reversed by growth hormone administration to a striking net release rate of 960 +/- 229 nmol.min-1.100 g-1, suggesting that glutamine nitrogen is spared incorporation into urea by shunting into glutamate and release into the blood.