Response to growth hormone therapy in experimental ischemic acute renal failure.
In acute renal failure (ARF), the gene and peptide expression of insulin-like growth factor-I (IGF-I) falls. Because IGF-I is regulated by growth hormone (GH) and because kidney GH receptor expression is also attenuated in ARF, the impaired IGF-I expression may partly reflect local GH resistance. Because IGF-I treatment accelerates recovery from ARF, we determined whether high-dose GH therapy could overcome this putative GH resistance, stimulate IGF-I production, and enhance recovery. Rats with ARF were given 2.5 mg GH or vehicle (V) over 2 days, beginning 24 hours before the onset of ARF. GH prevented weight loss but did not modify the course of ARF. Next we determined whether the failure of GH to modify kidney recovery could reflect a failure to stimulate renal IGF-I gene expression. Rats were treated with GH or V over an 18-hour period beginning 1 day after the induction of ARF. Hepatic IGF-I mRNA and serum IGF-I peptide levels rose significantly with GH treatment, but the low kidney IGF-I mRNA levels did not respond. We conclude that the failure of GH to enhance recovery from ARF is caused by impaired GH-stimulated renal IGF-I production, while the maintenance of body weight likely reflects the systemic effects of the increase in hepatic IGF-I production.
Fervenza
F C
FC
Research Service, Veterans Affairs Palo Alto Health Care System, California 94304, USA.
Hsu
F W
FW
Tsao
T
T
Friedlaender
M M
MM
Rabkin
R
R
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D013006:Growth Hormone / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003404:Creatinine