Effects of growth hormone on steroid-induced increase in ability of urea synthesis and urea enzyme mRNA levels.
Growth hormone (GH) reduces the catabolic side effects of steroid treatment due to its effects on tissue protein synthesis/degradation. Little attention is focused on hepatic amino acid degradation and urea synthesis. Five groups of rats were given 1) placebo, 2) prednisolone, 3) placebo, pair fed to the steroid group, 4) GH, and 5) prednisolone and GH. After 7 days, the in vivo capacity of urea N synthesis (CUNS) was determined by saturating alanine infusion, in parallel with measurements of liver mRNA levels of urea cycle enzymes, N contents of organs, N balance, and hormones. Prednisolone increased CUNS (micromol . min-1 . 100 g-1, mean +/- SE) from 9.1 +/- 1.0 (pair-fed controls) to 13.2 +/- 0.8 (P < 0.05), decreased basal blood alpha-amino N concentration from 4.2 +/- 0.5 to 3.1 +/- 0.3 mmol/l (P < 0.05), increased mRNA levels of the rate- and flux-limiting urea cycle enzymes by 20 and 65%, respectively (P < 0. 05), and decreased muscle N contents and N balance. In contrast, GH decreased CUNS from 6.1 +/- 0.9 (free-fed controls) to 4.2 +/- 0.5 (P < 0.05), decreased basal blood alpha-amino N concentration from 3. 8 +/- 0.3 to 3.2 +/- 0.2, decreased mRNA levels of the rate- and flux-limiting urea cycle enzymes to 60 and 40%, respectively (P < 0. 05), and increased organ N contents and N balance. Coadministration of GH abolished all steroid effects. We found that prednisolone increases the ability of amino N conversion into urea N and urea cycle gene expression. GH had the opposite effects and counteracted the N-wasting side effects of prednisolone.
Department of Medicine V, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
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Grøfte
D S
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Jensen
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Grønbaek
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Wolthers
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Jensen
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Tygstrup
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Vilstrup
D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D001123:Argininosuccinate Lyase / Q000096:biosynthesis; D001124:Argininosuccinate Synthase / Q000096:biosynthesis; D001835:Body Weight / Q000187:drug effects; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000096:biosynthesis; D015342:DNA Probes; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009928:Organ Specificity; D009954:Ornithine Carbamoyltransferase / Q000096:biosynthesis; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism*
D015342:DNA Probes; D012333:RNA, Messenger; D014508:Urea; D013006:Growth Hormone; D011239:Prednisolone; D009954:Ornithine Carbamoyltransferase; D001119:Arginase; D001123:Argininosuccinate Lyase; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase