Control of liver and kidney growth

The control of compensatory growth in liver and kidney has been studied with particular reference to the early events in the process. It has been shown that immediately after unilateral nephrectorhy there is no significant change in the glomerular filtration rate of the surviving kidney, though its blood supply increases by about 25%. As might be anticipated, an animal which has thus suffered a loss of half its renal function shows accumulation of urea and creatinine in its plasma. Perhaps surprisingly, on the other hand, the operation appears to cause no serious metabolic upset since plasma amino acid levels where remarkably unaffected. Changes in renal function concomitant with the kidney growth produced by feeding a high-gelatin diet for three days were compared with the changes accompanying compensatory renal hypertrophy. The high-gelatin diet caused a significant elevation of glomerular filtration rate but an even greater increase in kidney weight. Contrary to unilateral nephrectomy the high-gelatin diet did not result in an increase in renal blood flow. A preliminary investigation was made of the biochemical events in the early stages of compensatory renal hypertrophy. Measurements of RNA synthesis in vivo, RNA polymerase, DNA polymerase and heterodisperse nucleoplasmic RNA metabolism showed no marked changes. The accumulation of RNA, detectable after 12 hours, is the first unequivocal sign that kidney growth is under way. This increase in RNA content can be abolished if the animal is kept anaesthetised from operation until sacrifice. The possibility of the use of the enzyme ornithine decarboxylase as an early indicator of growth was investigated. It was found to increase 90-fold in activity early during liver regeneration and was maintained at an elevated level for at least 48 hours. Similar but transient increases were also produced by 10% hepatectomy and sham operation. Unilateral nephrectomy resulted in a transient peak of ornithine decarboxylase activity in the remaining kidney 4 hours after operation but sham operation produced a similar but somewhat smaller response. The latter response to operative stress could be abolished by treatments affecting glucocorticoid secretion. Dexamethasone, a potent glucocorticoid, markedly stimulated kidney ornithine decarboxylase activity. However, in addition to the response to stress there was an added increase in enzyme activity at 4 hours, attributable to the process of compensatory growth, both in liver and kidney. Analysis of plasma corticosterone showed that unilateral nephrectomy and sham operation were equally stressing. Ornithine decarboxylase was found to be much higher in the kidney than in all other tissues examined except prostate. In contrast the levels of the enzyme S-adenosylmethionine decarboxylase, which is thought to be coupled to polyamine biosynthesis, were found to be comparable in liver and kidney. However, no marked changes in S-adenosylmethionine decarboxylase could be demonstrated during the first 24 hours of compensatory renal hypertrophy. The .relationship of ornithine decarboxylase activity to growth was investigated in C13 cells in culture. The enzyme was high in exponentially growing cells but low in 'resting,' cells. Stimulation of 'resting' cells to growth resulted in a sharp peak in ornithine decarboxylase activity