Hypophysectomy decreases and growth hormone increases the turnover and mass of rat liver glutamine synthetase

Hypophysectomy diminishes rat liver glutamine synthetase (GS) activity and growth hormone (GH) administration restores this activity to normal levels; brain GS is unaffected. We have now investigated the effects of long-term hypophysectomy (45-day) and GH treatment on the GS mass (amount of enzyme) and turnover in rat liver and brain. Labeled GS was isolated by immunoprecipitation at intervals between one and six days after pulse administration of U-14C] leucine and the GS half-life (t1/2) was determined. The GS mass was obtained by immunoassay and by calculation using the specific activity of purified GS. GS turnover was calculated by multiplying the GS mass by the first-order rate constant of degradation (kd). During the time course of each experiment, the GS mass did not change, indicating that in each of the three hormonal states studied, a steady state existed. Hypophysectomy increased the t1/2 of hepatic GS from 3.8 to 8.8 days and decreased GS turnover from 0.38 to 0.1 microgram/100 g body wt/day; the GH regimen used restored the turnover to above normal levels, 0.6 microgram/100 g body wt/day. The GS mass decreased from 2.0 to 1.2 micrograms/100 g body wt and GH restored the GS mass to normal levels. The brain enzyme was not affected by hypophysectomy or GH.