Growth hormone therapy in calcium-loaded rats with renal failure.
GH increases linear growth in children with chronic renal failure, but the response remains suboptimal in some patients. Some of the factors that may explain the poor response to GH include high doses of calcitriol and exogenous calcium loading to prevent hyperphosphatemia. High doses of exogenous calcium adversely affect chondrocyte proliferation and delay mineralization in the growth plate of rats with renal failure; bone histomorphometric changes in these animals are comparable to adynamic bone. To evaluate GH effects on adynamic bone in renal failure, 48 weanling rats underwent sham nephrectomy (Intact-Control) or 5/6 nephrectomy (Nx). Nx animals were fed a high-calcium diet (Nx-Ca(2+)) to induce adynamic bone. After 4 wk, the Nx-Ca(2+) animals were treated with GH (Nx-Ca(2+) + GH), calcitriol (Nx-Ca(2+) + D), or a combination of GH and calcitriol (Nx-Ca(2+)GH + D) for 2 wk. Serum intact PTH and IGF-I levels did not differ among all nephrectomized groups given high calcium. GH did not increase body length or tibial length at the end of study period. In the proximal tibia, the width of the growth plate and the growth plate architecture did not improve with GH. There was a decline in histone-4 expression, IGF-I protein, IGF binding protein-3, and bone morphogenetic protein-7 staining and a mild increase in IGF-I receptor, GH receptor, and gelatinase B expression in the Nx-Ca(2+) + GH group when compared with the Intact-Control group. Calcitriol blunted some of the mitogenic effects of GH in the growth plate. Thus, there was a poor response to GH therapy in calcium-loaded animals with renal failure.
Sanchez
Cheryl P
CP
Department of Pediatrics, University of Wisconsin Medical School, 1300 University Avenue, Madison, Wisconsin 53706, USA. cpsanchez@wisc.edu.
He
Yu-Zhu
YZ
D000818:Animals; D001824:Body Constitution; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation; D002455:Cell Division; D019902:Chondrocytes / Q000166:cytology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000494:pharmacology*; D006132:Growth Plate / Q000187:drug effects; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism
D024043:Collagen Type II; D006657:Histones; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D013006:Growth Hormone; D002118:Calcium