Effects of growth hormone and insulin-like growth factor-I singly and in combination onin vivocapacity of urea synthesis, gene expression of urea cycle enzymes, and organ nitrogen contents in rats

Abstract

fect on the capacity of urea synthesis is caused by a Improvement of nitrogen balance is desirable in padecreased translation rate of the urea cycle enzymes tients with acute or chronic illlness. Both growth horcaused by GH and IGF-I's down-regulatory effect on urea mone (GH) and insulin-like growth factor-I (IGF-I) are cycle enzyme gene transcription. The findings may indipromising anabolic agents, and their combined adminiscate a novel mechanism of the protein anabolic action tration has been shown to reverse catabolism more effiof GH and IGF-I. (HEPATOLOGY 1997;25:964-969.) ciently than each of the peptides alone. This is believed to be mediated primarily through increased peripheral protein synthesis, whereas little attention has focused Improvement of nitrogen balance is desirable in patients on a possible participation of amino acid metabolism in with acute or chronic illness, and growth hormone (GH) is a the liver. Four groups of rats were given: 1) placebo; 2) promising anabolic agent.1-4 However, it cannot reverse nitro-GH (200 mg/d); 3) IGF-I (300 mg/d); and 4) both GH and gen wasting in all catabolic situations, and it may cause hy-IGF-I. After 3 days, the maximum capacity of urea-nitro-perglycemia and insulin resistance, which limits its clinical gen synthesis was determined by saturating infusion of use.5-7 Insulin-like growth factor I (IGF-I) mediates some of alanine (n Å 8 in each group), together with measure-the growth-promoting effects of GH and has been reported ments of liver messenger RNA (mRNA) levels for urea to cause an anabolic response comparable with that of GH, cycle enzymes (n Å 5 in each group) and N-contents of but it may induce hypoglycemia.8 When using GH and IGFmuscles, heart, and kidney. Basal plasma a-amino acid I simultaneously, Kupfer et al. observed an enhanced effect concentrations were similar in all groups. The capacity on overall nitrogen excretion compared with either peptide of urea-N synthesis [mmol/(min 1 100 g body weight)] alone. 9 was reduced in a stepwise manner (placebo: 8.25 { 1.2;As for the anabolic mode of action of the peptides, little GH treatment: 6.52 { 0.8; IGF-I treatment: 5.5 { 0.6; and attention has focused on the possible role of amino acid me-GH/IGF-I: 4.22 { 1.6 [P õ .001 by ANOVA]), each step tabolism in the liver, although administration of GH and, in being lower than the former. Serum IGF-I increased particular, IGF-I reduces blood urea nitrogen. [10][11][12] There are stepwise from placebo (699 { 40 to 1,579 { 96 mg/L in the conflicting data regarding the influence of GH on hepatic combined GH/IGF-I group), and was correlated nega-nitrogen metabolism. Pacatti et al. found that GH decreases tively with the capacity of urea-nitrogen synthesis (P õ hepatic uptake of amino acids in humans and rats, 11 whereas .01). mRNA levels for urea cycle enzymes in the liver Palekar et al. found that GH decreases the activities of urea decreased after GH and IGF-I treatment, and the effect cycle enzymes in rat liver. 12 In humans, we found unchanged was more ...

Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats

“…In the present study the metabolic effects of Ipamorelin were similar to previous studies with GH and IGF-I treatment of normaland steroid treated rats [2,7,25,32]. In the present study, liver nitrogen content in the pair-fed controls is larger than in a previous study, whereas the other variables are similar [2].…”

“…suggest that a significant part of the catabolic effects of prednisolone and the anabolic effects of GH and Ipamorelin probably involves regulation of urea synthesis on gene level. The anabolic actions of GH are partly due to stimulation of hepatic release of IGF-I, and we have earlier described a direct effect of IGF-I on hepatic urea synthesis and regulation of urea cycle enzymes in rats [25]. There are conflicting reports as to the effects of GH secretagogues on IGF-I levels [8,[26][27][28][29].…”

Seasonal regulation of the growth hormone-insulin-like growth factor-I axis in the American black bear (Ursus americanus)

“…GH treatment reduced levels of BUN but not creatinine, indicating that this change in BUN reflects an effect on nitrogen metabolism and not renal function. GH treatment may reduce levels of BUN by several mechanisms by both suppressing mobilization of protein stores (13) and reducing amino acid catabolism and urea production at the level of the liver (12). Based on levels of IGF-I, the effects of endogenous GH appear to be at their nadir during early denning, indicating that GH probably does not play a major role in maintaining nitrogen balance during this phase of winter denning.…”

Arginine Deprivation as a Targeted Therapy for Cancer

“…Several investigators have demonstrated that glucocorticoid, glucagon and cyclin AMP increase ASS expression whereas fatty acids repress ASS expression [58][59][60][61][62][63][64][65]. Insulin and growth hormone have negative influence on ASS in liver tissue but no effect in other tissue [66][67][68]. Cytokines, IL-Ib, interferon and TGF-b also can influence ASS expression [69,70].…”