Effects of rhGH and rhIGF-1 on renal growth and morphology

Abstract

It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawley rats, we measured the effects of rhGH and rhIGF-1 and their combination by the following parameters: kidney weight/body weight ratio, DNA/protein ratio, mRNA of GH receptor and of IGF-1, mitosis index and PCNA (by immunohistology), zonal architecture and glomerular diameter by micromorphometry. Both rhGH and rhIGF-1 dose-dependently increased renal weight and body weight over vehicle treated controls. With rhGH, liver dry weight/body weight ratio increased, but kidney dry weight/ body weight ratio remained unchanged (0.99 ± 0.06 × 10-3 vs. 1.02 ± 0.07 in vehicle controls). In contrast, a significant increase of kidney dry weight/body weight ratio was seen in rats treated with rhIGF-1 (1.3 ± 0.21 × 10-3). Addition of high doses of rhGH to high doses of rhIGF-1 caused no further increase of the ratio despite a significant further increase of body weight. rhGH increased the abundance of renal GH receptor mRNA (0.46 ± 0.32 amol/μg DNA vs. 0.08 ± 0.07 in controls) and of IGF-1 mRNA (1.35 ± 0.5 pg/μg DNA vs. 0.35 ± 0.17), whereas no change was seen with IGF-1 treatment. rhGH and rhIGF-1 increased kidney DNA/protein ratio, mitoses and PCNA expression in various renal structures. Further stimulation of mitoses by rhGH was seen even after subtotal nephrectomy, which was associated with markedly stimulated baseline proliferation of renal cells. The results document that rhGH increases renal weight in proportion to body weight while rhIGF-1 increases it out of proportion to body weight. Both peptides increase renal glomerular and tubular cell proliferation and renal DNA/protein ratio. This observation points to a major role of hyperplasia in renal weight gain of young female animals treated with the peptides. The size of glomeruli increased, but the increment was in proportion to body weight. Glomerulosclerosis was not detected even after 60 days of treatment with rhGH or with rhIGF-1.