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      Differential Responses of Circulating Prolactin, GH, and ACTH Levels and Distribution and Activity of Submaxillary Lymph Node Lymphocytes to Calorie Restriction in Male Lewis and Wistar Rats

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          Objectives: Calorie restriction has been associated with anorexia in growing individuals, but the mechanisms involved are not known. Also, the effects of carbohydrates and lipid restriction in growing individuals were not studied. The aim of this study was to determine whether 66% calorie restriction (lipids and carbohydrates) differentially affects growing rats of the Wistar or Lewis strains. Methods: Growing male Wistar and Lewis rats were subjected to 66% calorie restriction for 4 weeks. Plasma prolactin, growth hormone (GH), and adrenocorticotropic hormone (ACTH) levels were measured by specific radioimmunoassays. Likewise, lymphocytes from submaxillary lymph nodes were aseptically obtained to study absolute number of lymphocytes, cell surface markers (CD4+, CD8+, CD4+CD8+, B, and T cells), and proliferation. Results: The body weight gain was lower in Lewis than in Wistar rats and was blunted in both strains by calorie restriction. Wistar and Lewis rats exhibited differential patterns of plasma prolactin, ACTH, and GH levels as well as proliferative capacities of T and B cells and their distribution in the submaxillary lymph nodes. Calorie restriction increased plasma prolactin and ACTH levels in Lewis as compared with Wistar rats. However, the plasma GH levels were diminished in both strains of rats by calorie restriction. All changes in plasma prolactin ACTH and GH levels seemed to correlate with the modifications observed in the distributions of T and B subsets in the submaxillary lymph nodes as well as in their proliferative capacity. Conclusions: Calorie restriction differentially modifies the secretory patterns of prolactin, GH, and ACTH in Lewis and in Wistar rats. These changes may explain, at least in part, the associated modifications in the proliferative capacity of submaxillary lymph node lymphocytes and in their distribution.

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          Most cited references 15

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          Gene expression profile of aging and its retardation by caloric restriction.

          The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals. Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.
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            Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents.

            Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximately 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents.
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              Social stress in laboratory rats: hormonal responses and immune cell distribution.

              Previous experiments with chronically coexisting groups of Long-Evans rats indicated differences in many aspects of blood cellular immunity between winner and loser rats. The present study investigated the specific hormonal response patterns of winners and losers in relation to changes in numbers of blood immune cells. At the beginning of a 7 day period of chronic confrontation, a partition wall was removed between two neighboring rat groups, each containing a male-female pair. Fights for dominance between the males resulted in fast establishment of stable dominance relationships. At day 7 of the confrontation, winner males showed stable concentrations of CBG (corticosteroid-binding globulin) and even reduced titers of total CORT (corticosterone). In contrast, a marked decrease in CBG and unaffected total CORT concentrations were determined in loser males. Increased norepinephrine (NE) and epinephrine (E) titers were evident only in losers. In addition, reduced testosterone titers were observed in the bitten loser male subgroup. All male subgroups lost body mass with most pronounced reductions in loser males. Confrontation caused a marked granulocytosis, especially in loser males. NE concentrations in loser males correlated with the percentage of granulocytes. Numbers of CD4 T-cells were lowered in all loser males and in non-biting winners. In not-bitten losers also a reduced number of CD8 T-cells was determined. Interestingly, higher pre-confrontational NE titers were detected in future bitten loser and future biting winner males relatively to not-bitten losers and non-biting winners. The present report indicates that differential hormonal response patterns may play an important role in some of the immunological differences observed between winner and loser males under stressful social conditions.

                Author and article information

                S. Karger AG
                July 2004
                09 July 2004
                : 11
                : 4
                : 247-254
                Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain
                78443 Neuroimmunomodulation 2004;11:247–254
                © 2004 S. Karger AG, Basel

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                Figures: 5, References: 47, Pages: 8
                Original Paper


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