Morphological changes in the kidney of dogs chronically exposed to exogenous growth hormone.
Porcine growth hormone was administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/d for 14 weeks, markedly elevating serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. This was accompanied by a significant increase in body weight gain and kidney weights in both male and female dogs. The increase in kidney weight (6 to 54%) was slightly greater than the increase in body weight (6 to 40%). By light microscopy, glomerular deposits, mesangial thickening, and very slight cellular infiltration in glomeruli were seen in mid- and high-dose groups. Based on morphometric evaluation, there was an increase in the renal glomerular area, which was statistically significant (p < or = 0.05) in the mid- and high-dose males and in the high-dose females. This was associated with a statistically significant (p < or = 0.05) increase in the number of total glomerular cells in the mid- and high-dose males. By transmission electron microscopy, thickening of the glomerular basal lamina and diffuse increase of the mesangial matrix were observed in both male and female dogs in the mid- and high-dose groups. Immunohistochemical reactions were negative for IgG, IgM, and C3. The morphological changes in the kidney of dogs resemble the diffuse glomerulosclerosis described in human diabetic nephropathy.
Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, Riom, France.
S
S
Molon-Noblot
P
P
Laroque
S
S
Prahalada
L G
LG
Stabinski
C P
CP
Peter
P
P
Duprat
M J
MJ
van Zwieten
D000818:Animals; D004285:Dogs; D005260:Female; D013006:Growth Hormone / Q000633:toxicity*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D012727:Sex Characteristics; D013552:Swine
D013006:Growth Hormone