ROWE. Hypoxia and malnutrition in newborn rats: effects on RNA, DNA, and protein in tissues. Am. J. Physiol. 217(3): 642-645. 1969.-Newborn male rats were exposed to 12% oxygen from 1 to 7 days and their brain weights, DNA, protein, or RNA content studied at 7, 21, or 35 days. At 35 days, studies were made of cerebrum and cerebellum and of the liver, muscle mass, carcass fat, and skeletal collagen. These rats were compared with normal rats and with rats malnourished from 1 to 7 days. Hypoxia caused a failure of brain DNA and protein content to increase. At 35 days, the hypoxic rats had reduction in body weight, cerebellar weight, liver weight, muscle mass, muscle cell number, and skeletal collagen. There was an increase in carcass fat. The cerebellar DNA and protein content were reduced whereas in the cerebrum, liver, and muscle, the RNA content was very low (not measured in cerebellum). It is concluded that during hypoxia cell multiplication is prevented, but subsequently there is interference with RNA production and protein synthesis with growth retardation. In the brain the cerebellum is damaged more than the cerebrum. The effects of hypoxia can not be ascribed entirely to restricted food intake.

ExtractFollowing weaning, Sprague Dawley rats were given 60% of a normal Purina chow intake until 7 weeks of age. There was a reduced DNA content in the cerebrum at 49 days of age. Previous failure to demonstrate reduced DNA content in rat brain during undernutrition could relate to preoccupation with whole brain analysis. The present study indicates that cerebral DNA increases in normal rats after weaning.T h e cell size or the ratio of protein: DNA increased in the muscle tissues of rats subjected to the caloric restriction, while the ratio of RNA:DNA increased in all tissues studied. These findings are contrary to those found in protein deficiency per se. Carcass weight, fat, and water were below expected levels, but skeletal collagen was less affected.Rats from 26 to 38 days of age, given an increased insulin-induced caloric intake, showed an excess weight gain per gram of food consumed per day and an excess growth of muscle and fat. In contrast, cerebral weight, water, protein, DNA, and RNA content were reduced possibly because of periodic hypoglycemia. SpeculationFollowing weaning, rats subjected to sustained caloric restriction have reduced cell numbers for age and are said not to reach expected cell populations on rehabilitation. With caloric restriction, growth hormone may no longer be effective at the cellular level, but insulin activity continues. Although the ratio of cytoplasm: nucleus is maintained, DNA replication is minimal. Alternatively, since DNA content in the cerebrum decreases, hypothalamic or acidophilic cells may be lost, and growth hormone production may be insufficient for adequate DNA replication and somatic growth.When protein is restricted, the failure of cells to increase in size may be associated with atrophy of the pancreas and a decrease in insulin production.Introduciion nutrition in the sucking pig from 2 weeks to one year of age produced a decrease in DNA synthesis in the Malnutrition is widespread throughout the world. brain, which failed to attain expected levels after reThere have been many studies of metabolic changes in habilitation.

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.

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Binding of human (hGH) and bovine (bGH) GH and ovine PRL (oPRL) has been compared in liver membranes from GH-deficient dwarf "little" mice (lit/lit) and their normal-sized littermates (lit/+). Binding of [125I]hGH to lit/lit membranes was dependent on time, temperature, and membrane concentration and was reversible. Scatchard plots of the binding of [125I]hGH to male and female lit/lit and lit/+ membranes were linear, with no significant differences between binding affinities (overall mean +/- SE, 1.42 +/- 0.27 X 10(9) M-1; n = 24). The hormonal specificity of binding was complex, with hGH being displaced by both somatotropic (bGH) and lactogenic (oPRL) competitors, indicating the presence of a mixed population of receptors. This conclusion was supported by the specific binding of both [125I]bGH and [125I]oPRL to membranes from male and female lit/lit and lit/+ mice. No differences in the specific binding of [125I]bGH to any membrane type was observed, indicating that GH receptors were at normal levels in lit/lit mice despite their deficiency of pituitary and serum GH. A sex difference in hGH and oPRL binding was seen only in normal (lit/+) mice. Male and female lit/lit mice exhibited the same degree of binding as normal female mice. These studies have demonstrated that dwarf little mice have normal levels of hepatic GH and PRL receptors, with binding characteristics not different from those of normal mice. Thus, it would appear that the mechanism of regulation of GH receptors by GH itself is different in this animal model of GH deficiency than in the Snell dwarf mouse and the hypophysectomized rat, where GH receptor levels are very low or absent. The failure of lit/lit mice to grow normally despite normal levels of GH receptor raises questions regarding the site and mechanism of the growth defect in the little mouse.