Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.
OBJECTIVE
Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism.


METHODS
Five groups of rats were included: (1) free-fed controls (2) pair-fed controls (3) prednisolone (delcortol, 4 mg x kg(-1) x day(-1)) (4) prednisolone and GH (1 mg x kg(-1) x day(-1)) (5) prednisolone and Ipamorelin (0.5 mg x kg(-1) x day(-1)). After seven days the hepatic capacity of urea-N synthesis (CUNS) was determined in parallel with measurements of liver mRNA levels of urea cycle enzymes, whole-body N-balance, and N-contents of various organs.


RESULTS
Compared to pair-fed controls, prednisolone increased CUNS (p<0.01) as well as the expression of urea cycle genes (p<0.01), and decreased N-balance (p<0.01) as well as organ N-contents (p<0.05). Compared to prednisolone treated animals, co-administration of GH reduced CUNS by 33% (p<0.01), normalized urea cycle gene expression, improved N-balance 2.5-fold, and normalized or improved organ N-contents. In prednisolone treated rats Ipamorelin reduced CUNS by 20% (p<0.05), decreased the expression of urea cycle enzymes, neutralised N-balance, and normalized or improved organ N-contents.


CONCLUSIONS
Accelerated nitrogen wasting in the liver and other organs caused by prednisolone treatment was counteracted by treatment with either GH or its secretagogue Ipamorelin, though at the doses given less efficiently by the latter. This functional study of animals confirms that the GH secretagogue exerts GH related metabolic effects and may be useful in the treatment of steroid-induced catabolism.
Aagaard
Niels Kristian
NK
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, DK-8000 Aarhus C, Denmark. nielaaga@rm.dk
Grøfte
Thorbjørn
T
Greisen
Jacob
J
Malmlöf
Kjell
K
Johansen
Peter B
PB
Grønbaek
Henning
H
Ørskov
Hans
H
Tygstrup
Niels
N
Vilstrup
Hendrik
H
D000818:Animals; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D009929:Organ Size; D011239:Prednisolone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism*
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D014508:Urea; D013006:Growth Hormone; D011239:Prednisolone; D009584:Nitrogen