The action of insulin, growth hormone, and epinephrine on cell growth in liver, muscle, and brain of the hypophysectomized rat.

Abstract

Extract: This study explores changes in deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein, and water content of muscle, liver, and cerebrum in hypophysectomized rats and the effects of injecting growth hormone, insulin, or growth hormone with epinephrine conjointly over an eleven-day period. Male hypophysectomized rats, 26 to 49 days of age, fed an ad libitum diet were studied. At 38 days of age they were injected with insulin, 0.4 to 1.8 units per day, with bovine growth hormone (250 μUg/day) or with the same amount of growth hormone and epinephrine, 5 to 20 μUg/day, concomitantly, or were untreated until the 49th day of age. Control rats of the same age were either pair-fed to untreated hypophysectomized rats or given an ad libitum diet. Untreated hypophysectomized rats showed poor body weight gain per unit food intake and reduced skeletal growth. The nucleic acid and protein content of liver, muscle, and cerebrum was reduced when compared with controls of the same age. The ratio of protein: DNA (cell size) was increased for body size but reduced for age. Administration of insulin caused hypertrophy of liver cells and increased the protein content of liver, but did not affect muscle and cerebrum. DNA content of liver or cerebrum did not increase, and the gain in DNA content of muscle was not remarkable. There was a definite increase in RNA content of muscle, liver, and cerebrum and in the ratios of RNA: DNA and protein: DNA of liver. Injections of growth hormone caused an increase in DNA (cell number), RNA, and protein content in liver, muscle, and cerebrum. There was a reduction in the ratio of cytoplasm to nucleus. The protein increment was nullified by the injection of epinephrine in conjunction with growth hormone. DNA content of muscle and liver was increased, but not to the level produced by growth hormone alone. The increase in RNA content of liver, muscle, and cerebrum was again significant; the ratio of RNA: DNA increased only in liver. Caloric intake of untreated hypophysectomized rats and those treated with growth hormone or insulin was comparable. Rats injected with epinephrine showed a significant increase in caloric intake. The results indicate that insulin is involved with growth in cell size, while growth hormone is active with respect to the increase in cell number. Both hormones are required for optimal growth. Speculation: The present study indicates that both growth hormone and insulin are required for optimum cell growth. Epinephrine administration retards the increase in cell number that normally occurs in hypophysectomized rats receiving growth hormone. This suggests that overactivity of the sympathetic pathways may retard growth and produce effects that simulate hypopituitarism.