Juvenile (1 yr) and adult (3-5 yr) male rhesus monkeys (Macaca mulatta) and juvenile (1-4 yr) and adult (5-10 yr) male squirrel monkeys (Saimiri sciureus) were fed a diet at or near ad libitum levels based on recommended caloric intake for age and body weight or fed 30% less of the same diet with this restriction gradually introduced over a 3-mo period. Analysis of body weights among these respective control and experimental groups from the first year of the study indicated that the monkeys undergoing dietary restriction were gaining weight at a markedly slower rate compared to control values. Actual food intake among diet-restricted groups had been reduced 22-24% below control levels. Periodic analysis of hematology and blood chemistry measurements over the first year of the study detected few significant differences between control and experimental groups to indicate that diet restriction was not detrimental to general health. When values obtained from hematology and blood chemistry measurements of juvenile and adult groups (control and experimental groups combined) were compared to ad libitum fed old monkeys from each species (greater than 18 yr for rhesus; greater than 10 yr for squirrel monkeys), many significant age differences were noted. Among the largest and most consistent findings in both species were age-related decreases in concentrations of lymphocytes, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and phosphates as well as the albumin/globulin ratio and the blood urea nitrogen/creatinine ratio. Age-related increases in serum globulin and creatinine concentrations were also found. These parameters as well as many others being implemented in the study will be monitored further to determine if diet restriction affects the rate of development as well as aging as observed in numerous rodent studies applying such nutritional manipulations.
The concentrations of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. However, there is no physiologic evidence ofincreased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action ofcortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (=60 x 106 yr ago) and before the diversion of the New World primates from each other (-15 x 106 yr ago).End-organ resistance to steroid hormones has been described for androgens (1), aldosterone (2), progesterone (3), and vitamin D (4). There are no known examples of resistance to the action ofestradiol and only two examples ofresistance to cortisol. First, the guinea pig has long been known as a "corticoresistant" species (5); second, there is a single example ofresistance to cortisol in man (6, 7). Two New World primates, the squirrel monkey (Saimiri sciureus) (8) Lemurinae or Galaginae were studied. Plasma samples for assay of total and free cortisol, aldosterone, corticosterone, glucose, and electrolytes were obtained between 7:00 and 9:00 a.m. by femoral artery puncture under ketamine anesthesia. Plasma samples were drawn during the 10-to 20-min period of anesthesia. Preliminary studies showed that the plasma cortisol concentrations measured at 2-min intervals were stable during this period of time. Human plasma samples were obtained by venipuncture at the same time of the day and, despite the differences in the sampling, have been used for comparison.Total plasma cortisol (10) and plasma corticosterone (11), aldosterone (12), and dexamethasone (13) were measured by previously described radioimmunoassays. Plasma glucose was measured by the hexokinase method (14). The cortisol not bound to protein (i.e., free) was estimated by equilibrium dialysis at 370C with 1:5 diluted plasma as described (15, 16). The concentration of unbound cortisol was calculated by applying the formula of Slaunwhite (17) and was corrected for the initial dilution.Twenty-four hour urine samples were collected in metabolic cages. Urinary free cortisol was measured by radioimmunoassay as described (18), and 24-hr urinary excretion was calculated.The suppressibility of the hypothalamic-pituitary-adrenal axis was examined by administering dexamethasone sodium phosphate (Decadron). Decadron was given intramuscularly at 8:00 p.m. to squirrel and...
We tested for differences in aspects of mineral metabolism during the administration of diets with only vitamin D3 or only vitamin D2 in four nonhuman anthropoid primate species [two catarrhini, Macaca fascicularis (crab-eating macaque) and Macaca mulatta (rhesus macaque), and two platyrrhini, Saimiri sciureus (squirrel monkey) and Aotus vociferans (night monkey)]. All four species maintained approximately 2- to 3-fold higher serum 25-hydroxyvitamin D (25OHD) level while receiving vitamin D3 than while receiving similar amounts of vitamin D2. Serum 25OHD in M. mulatta receiving the standard primate dietary supplement of vitamin D3 was high enough (360 +/- 60 vs. 70 +/- 25 nM in vitamin D-supplemented humans; P less than 0.0001) to suggest that this widely used level of vitamin D3 supplementation is excessive for some M. mulatta. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] in A. vociferans was uniquely high [P less than 0.01; species mean, 19 +/- 5, 95 +/- 12, and 27 +/- 5 nM in groups receiving diets with 1.5 IU vitamin D3/g, 6.6 IU vitamin D3/g, and 15 IU vitamin D2/g, respectively; mean 24,25-(OH)2D from the other three species pooled across three diets was 7 +/- 5 nM]. We confirmed relative resistance to 1,25-(OH)2D in S. sciureus, manifested by osteomalacia and moderately high serum 1,25-(OH)2D. Serum 1,25-(OH)2D in S. sciureus increased 4-fold (P less than 0.05) when the precursor in serum was changed from 250HD3 to 250HD2, suggesting that this species shows more severe resistance to 1,25-(OH)2D2 than to 1,25-(OH)2D3. In conclusion, we found many differences in vitamin D metabolism among four nonhuman anthropoid primate species. The striking feature in A. vociferans (high, 24,25-(OH)2D without high 25OHD in serum independent of whether diet contained only vitamin D3 or only vitamin D2) should allow determination of whether 24,25-(OH)2D functions as a unique agonist or an inactive metabolite in this species.
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