Effects of growth hormone (GH) administration on functional hepatic nitrogen clearance: studies in normal subjects and GH-deficient patients.
A decline in serum urea levels and urinary urea excretion is usually seen after GH administration in humans, indicating overall protein anabolism. Whether this reflects the diminished supply of alpha-amino acids for urea synthesis or a substrate-independent hepatic mechanism is unknown. To pursue this we measured the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during, and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in total body water. The slope of the linear relationship between UNSR and circulating alanine levels represents the hepatic components of conversion of amino nitrogen and is denoted the functional hepatic nitrogen clearance (FHNC). Eight male volunteers were randomly investigated on three occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1 IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was significantly lower when the subjects were receiving GH therapy [maximum +/- SE, 133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2-day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/- 1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH-deficient adult patients were randomly studied twice: 1) on regular daily (at 2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2 days. The UNSR during alanine infusion was likewise significantly lower when the patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/- 9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic action of GH and show that short term GH deprivation is associated with catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a substrate-independent hepatic mechanism.
Wolthers
T
T
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark.
Grøfte
T
T
Jørgensen
J O
JO
Møller
N
N
Vahl
N
N
Christiansen
J S
JS
Vilstrup
H
H
D000328:Adult; D002352:Carrier Proteins / Q000032:analysis; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009584:Nitrogen / Q000378:metabolism*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D009584:Nitrogen