Hormones – Cytokines – Signaling
Kidney International (1999) 56, 2048–2054; doi:10.1046/j.1523-1755.1999.00776.x
Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent
Allan Flyvbjerg, William F Bennett, Ruth Rasch, Johan W Van Neck, Cora A H Groffen, John J Kopchick and John A Scarlett
Medical Department M, Medical Research Laboratory M, Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus C, Denmark; Sensus Drug Development Corporation, Austin, Texas, USA; Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark; Laboratory for Pediatrics, Erasmus University Rotterdam, Rotterdam, The Netherlands; and Edison Biotechnology Institute, Department of Biomedical Sciences, Ohio University, Athens, Ohio, USA
Correspondence: Allan Flyvbjerg, M.D., D.Sc., Medical Department M/Medical Research Laboratory M, Institute of Experimental Clinical Research, University Hospital, Kommunehospitalet, DK-8000 Aarhus C, Denmark. E-mail: allan.flyvbjerg@dadlnet.dk
Received 20 January 1999; Revised 15 June 1999; Accepted 19 July 1999.
Abstract
Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent.
Background
Growth hormone (GH) and insulin-like growth factors (IGFs) have been implicated as pathogenic factors in compensatory renal growth (CRG) following unilateral nephrectomy in rodents. CRG in adult rats has been suggested to be GH dependent and GH independent in immature rats. However, the exact role of GH as a regulating or permissive factor in CRG in adult rodents has not been fully resolved to date.
Methods
To elucidate a possible direct, permissive role of GH in CRG, we examined the effect of a newly developed specific GH receptor (GHR) antagonist (G120K-PEG) on kidney IGF-I accumulation and renal/glomerular hypertrophy over seven days after uninephrectomy in adult mice.
Results
Placebo-treated uninephrectomized mice were characterized by a transient increase in kidney IGF-I concentration preceding CRG and an increase in glomerular volume. In G120K-PEG–treated uninephrectomized animals, increased kidney IGF-I levels, kidney weight, and glomerular volume were fully abolished. No differences were seen between the two uninephrectomized groups with respect to body weight, food intake, blood glucose, serum GH, IGF-I, or IGFBP-3 levels.
Conclusions
The administration of a GHR antagonist in uninephrectomized adult mice has renal effects without affecting circulating levels of GH/IGFs, indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I accumulation through the renal GHR. This study shows, to our knowledge for the first time, that CRG in adult mice is strictly GH dependent.
Keywords:
growth hormone, antagonist, nephrectomy, insulin-like growth factors, mRNA
