The Action of Insulin, Growth Hormone, and Epinephrine on Cell Growth in Liver, Muscle, and Brain of the Hypophysectomized Rat[39]

Abstract

ExtractThis 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 a n eleven-day period.Male hypophysectomized rats, 26 to 49 days of age, fed an ad libitunz 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 pglday) or with the same amount of growth hormone and epinephrine, 5 to 20 pglday, 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 libitunz 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. T h e 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.T h e 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. SpeculationThe 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.

Skeletal Muscle Cell Mass and Growth: The Concept of the Deoxyribonucleic Acid Unit

“…The value of inspecting protein/DNA ratio in muscle and the number of nuclei within muscle mass can be illustrated further by considering certain abnormal situations. Studies on rats hypophysectomized at 21 days revealed at 35, 38, 49, and 56 days of age that there was no increment in the DNA content of muscle with time [18,23]. When tissue studies were carried out at 6 or 8 weeks of age, similar findings occurred in rats given Increments in number of nuclei in muscle of rats liypophysectomizcd at 21 days when treated from the 38th to 49lh day with various hormones.…”

“…That such is the case [3,18] is illustrated in Figure 7 (left side). This figure defines the changes in muscle when hypophysectomized rats are treated for 11 days with (a) bovine growth hormone, (b) protamine zinc insulin, or (c) growth hormone with reduced endogenous insulin [18].…”

Changes in Enzymes (GOT and GDH) and Metals (Zn, Mn, and Mg) in Liver of Rats During Endocrine Imbalance and Caloric Restriction

“…In conFurther reductions in trace metals per unit of DNA trast, hypophysectomized rats receiving growth hor-following injection of growth hormone were only signimone alone had a markedly increased protein content ficant for Zn. It is possible that some redistribution of in liver [4]. The additional injections of epinephrine new and existing cytoplasm occurs through establishand growth hormone did not change the content of ment of a higher polyploid series (tetraploid or octaMn per unit of DNA, but Zn and Mg per unit of DNA ploid cells), with relatively less, but adequate, amounts increased significantly (p <0.001).…”

“…Another interpretation may be that endogenous Absence of pituitary function reduces the amount of insulin is insufficient in relation to growth hormone. Zn, Mn, and Mg per unit of DNA in the liver of hypoIn the liver cell, the two hormones appear to act in physectomized rats in comparison with the amounts different directions, growth hormone affecting DNA of these metals per unit of DNA present in normal rats increase [I, 4,8,101 and insulin affecting protein acof the same weight. This finding indicates a true loss cretion [4].…”

“…Fluctuations in Zn appear to be more closely related to changes in cell RNA. RNA elevation is a precursor of protein synthesis [4,311, and Zn may be equally involved.…”