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Morphological Changes in the Kidney of Dogs Chronically Exposed to Exogenous Growth Hormone

Merck Sharp & Dohme-Chibret Laboratories, Research Center,Department of Safety Assessment, BP 134, Route de Marsat 63 203 Riom, France

Philippe Laroque

Merck Sharp & Dohme-Chibret Laboratories, Research Center,Department of Safety Assessment, BP 134, Route de Marsat 63 203 Riom, France

Srinivasa Prahalada

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Lea G. Stabinski

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Chennekatu P. Peter

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

Pierre Duprat

Merck Sharp & Dohme-Chibret Laboratories, Research Center,Department of Safety Assessment, BP 134, Route de Marsat 63 203 Riom, France

Matthew J. Van Zwieten

Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA

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 0.05) in the mid- and high-dose males and in the high-dose females. This was associated with a statistically significant (p 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.

Key Words: Kidney • growth hormone • pharmacological effect • morphometry • electron microscopy • insulin-like growth factor-1

Toxicologic Pathology, Vol. 28, No. 4, 510-517 (2000)
DOI: 10.1177/019262330002800402


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