Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment.
BACKGROUND
Children with chronic renal failure (CRF) exhibit growth retardation and a disturbed growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. Treatment of children with CRF with GH or GH/IGF-I can partially restore linear growth. The molecular basis for decreased longitudinal growth is not known but may involve an impaired action of GH.


METHODS
We used the growth-retarded uremic rat model to determine the abundance and distribution of GH receptors (GHRs) in the tibial epiphyseal growth plate and the influence of GH, IGF-I, or combined GH/IGF-I treatment. Pair-fed rats were used as the control.


RESULTS
While all treatment regimes increased body length and weight in both rat groups, only GH/IGF-I treatment increased the total growth plate width. This involved an increase in cell number in the hypertrophic zone, which could also be induced by IGF-I alone. Immunohistochemical analysis showed that uremic rats had decreased abundance of GHRs in the proliferative zone, and only GH/IGF-I therapy could overcome this decrease. These data thus suggest that growth retardation in uremic rats is, at least in part, due to a decrease in GHR abundance in chondrocytes of the proliferative zone of the tibial growth plate. This decreased GHR abundance can be overcome by combined GH/IGF-I therapy, thus enhancing generation and proliferation of hypertrophic zone chondrocytes and increasing growth-plate width.


CONCLUSIONS
These studies point to a mechanism for the growth retardation seen in children with CRF, and suggest that combined GH/IGF-I treatment may provide more effective therapy for these patients than GH alone.
Edmondson
S R
SR
Centre for Hormone Research, Royal Children's Hospital, Parkville, Victoria, Australia. edmondss@cryptic.rch.unimelb.edu.au
Baker
N L
NL
Oh
J
J
Kovacs
G
G
Werther
G A
GA
Mehls
O
O
D000818:Animals; D001835:Body Weight; D019902:Chondrocytes / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy; D013006:Growth Hormone / Q000494:pharmacology*; D006132:Growth Plate / Q000737:chemistry* / Q000166:cytology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000032:analysis*; D013977:Tibia / Q000737:chemistry* / Q000166:cytology / Q000254:growth & development; D014511:Uremia / Q000188:drug therapy / Q000503:physiopathology*
D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone