Effects of rhGH and rhIGF-1 on renal growth and morphology.
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 x 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 x 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/microgram DNA vs. 0.08 +/- 0.07 in controls) and of IGF-1 mRNA (1.35 +/- 0.5 pg/micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mehls
O
O
Department of Pediatrics, University of Heidelberg, Germany.
Irzynjec
T
T
Ritz
E
E
Eden
S
S
Kovàcs
G
G
Klaus
G
G
Floege
J
J
Mall
G
G
D000818:Animals; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics; D011994:Recombinant Proteins; D013997:Time Factors
D004338:Drug Combinations; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA