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Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent
A Flyvbjerg1, W F Bennett, R Rasch
1Medical Department M, Medical Research Laboratory M, Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus C, Denmark. allanflyvberg@dadlnet.dk
Unlabelled:
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.
Insights
Compensatory renal growth in adult mice after kidney removal is dependent on growth hormone (GH). Blocking the GH receptor prevents kidney enlargement and IGF-I increase, confirming GH
Area of Science:
- Nephrology
- Endocrinology
- Physiology
Background:
- Growth hormone (GH) and insulin-like growth factors (IGFs) are implicated in compensatory renal growth (CRG) after unilateral nephrectomy.
- Previous studies suggest CRG is GH-dependent in adult rats but GH-independent in immature rats.
- The precise role of GH in CRG in adult rodents remains unclear.
Purpose of the Study:
- To investigate the direct, permissive role of GH in CRG in adult mice.
- To determine if GH receptor antagonism affects kidney IGF-I accumulation and renal hypertrophy post-uninephrectomy.
Main Methods:
- Adult mice underwent uninephrectomy.
- A GH receptor (GHR) antagonist (G120K-PEG) or placebo was administered.
- Kidney IGF-I levels, renal/glomerular hypertrophy, body weight, food intake, and blood parameters were assessed over seven days.
Main Results:
- Uninephrectomized mice showed increased kidney IGF-I and glomerular volume.
- GHR antagonist treatment abolished these increases, preventing kidney weight and glomerular hypertrophy.
- Systemic parameters like body weight, blood glucose, and circulating GH/IGF-1 levels remained unaffected.
Conclusions:
- GH receptor antagonism inhibits renal IGF-I accumulation and CRG in adult mice.
- This effect appears mediated by direct inhibition of renal IGF-I through the renal GHR.
- This study demonstrates that CRG in adult mice is strictly GH-dependent.