Reduced food intake is the main cause of low growth hormone receptor expression in uremic rats.
To examine the respective effects of reduced food intake and of uremia on the growth defect in uremic rats, we have studied the expression of GH receptors in three groups of male rats: Group 1, rats fed ad libitum; Group 2, food-restricted to be pair-fed with uremic rats; Group 3, uremic rats. Animals were studied for a time period of 9 days starting 1 week after surgery (sham operation in rats of Groups 1 and 2, 5/6 nephrectomy in rats of Group 3). The gain in body length and weight of pair-fed controls and of uremic rats was comparable and significantly lower than that of rats fed ad libitum. IGF-1 plasma levels were low in rats of groups 2 and 3. Low food intake (50% that of rats fed ad libitum) resulted in a reduced number of GH receptors in liver membranes and a low plasma level of GH-binding protein (GHBP); GH receptor gene expression in the liver, as analyzed by Northern blots, was not significantly lower in normal food-restricted animals. In uremic rats, the low level of GH binding to liver membranes was comparable to that found in pair-fed controls; but the level of GHBP activity was normal, not different from the values found in rats fed ad libitum. However, expression of the liver GHBP mRNA was reduced in uremic rats. In uremia, the GH receptor dysfunction is not only at a transcriptional level but also at a post-transcriptional level. These findings suggest that uremia, as such, is not primarily responsible for the growth failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Villares
S M
SM
INSERM Unité 344, Endocrinologie Moléculaire, Hôpital Necker Enfants-Malades, Paris, France.
Goujon
L
L
Maniar
S
S
Delehaye-Zervas
M C
MC
Martini
J F
JF
Kleincknecht
C
C
Postel-Vinay
M C
MC
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D004435:Eating; D015870:Gene Expression; D006130:Growth Disorders / Q000209:etiology; D013006:Growth Hormone / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D014511:Uremia / Q000150:complications / Q000378:metabolism*
D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013006:Growth Hormone; C051815:somatotropin-binding protein