Yoshiyuki Hayashi

Renal pathology in rats bearing tumour-secreting growth hormone

The effects of growth hormone (GH) on renal structure and function were investigated in rats aged 10–16 weeks bearing a tumour secreting GH. Body weight gain, food intake, urine volume, and urinary excretion of cretinine and urea nitrogen were significantly greater in tumour-bearing rats than in controls. The tumour-bearing rats presented progressive proteinuria, hyperproteinaemia, and hyperlipidaemia. Creatinine clearance was significantly higher in experimental animals during the early experimental stage, but decreased as the glomerular lesions progressed, associated with a rise in serum creatinine levels. The glomeruli became progressively enlarged with degenerative changes of the visceral epithelial cells and capsular adhesions. In advanced stages proteinaceous material invaded the subcapsular space and the capillary lumen collapsed finally leading to glomerulosclerosis. Except for the presence of proteinaceous material and damaged epithelial cells the glomerular lesions resemble those observed experimentally after reduction of renal mass, and in diabetes mellitus. We speculate that the pathological features described are due to effects of persistently high levels of circulating GH on the glomerular cells.

Effect of ascorbic acid deficiency on calcium metabolism in bone of rat with hereditary defect in L-ascorbic acid biosynthesis

A strain of Wistar rat with a hereditary defect in L-ascorbic acid biosynthesis named osteogenesis disorder (OD) rat was used to explore the effect of ascorbic acid deficiency on bone metabolism. OD rats showed lower levels of serum phosphorus, alkaline phosphatase and urinary hydroxyproline than normal rats. Bone histological studies revealed that the essential feature of OD rats was the failure of bone formation. Very few osteoblasts were seen, but mineralization per se seemed to occur normally despite impaired formation of a new matrix. The cAMP response of the bone to parathyroid hormone (PTH) was examined, using isolated perfused femora. Cyclic AMP response to PTH was significantly lower in OD rats than in normal rats.OD rats showed a histological picture with severely reduced bone formation and impaired cAMP response to PTH, which suggests that ascorbic acid deficiency might induce osteoblastic insufficiency. OD rats provide us a useful animal model to study the effect of ascorbic acid deficiency on bone metabolism.