Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment.

Edmondson, Stephanie R. and Baker, Naomi L. and Oh, Jun and Kovács, Gábor and Werther, George A. and Mehls, Otto (2000) Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment. KIDNEY INTERNATIONAL, 58 (1). pp. 62-70. ISSN 0085-2538

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Abstract

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. CONCLUSION: 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.

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