Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia.
In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair-fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Tönshoff
B
B
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Edén
S
S
Weiser
E
E
Carlsson
B
B
Robinson
I C
IC
Blum
W F
WF
Mehls
O
O
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014511:Uremia / Q000378:metabolism*
D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein