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

Background. Children with chronic renal failure (CRF) exhibit growth retard ation 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 re store 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 abun dance and distribution of CH receptors (GHRs) in the tibial epiphyseal grow th plate and the influence of GH, IGF-I, or combined GH/IGF-I treatment. Pa ir-fed rats were used as the control. Results. While all treatment regimes increased body length and weight in bo th rat groups, only GH/IGF-I treatment increased the total growth plate wid th. This involved an increase in cell number in the hypertrophic zone, whic h 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 s uggest 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 th e tibial growth plate. This decreased GHR abundance can be overcome by comb ined GH/IGF-I therapy, thus enhancing generation and proliferation of hyper trophic zone chondrocytes and increasing growth-plate width. Conclusion. These studies point to a mechanism for the growth retardation s een in children with CRF, and suggest that combined GH/IGF-I treatment may provide more effective therapy for these patients than GH alone.