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Melanie Tran, Linda A Gallo, Andrew J Jefferies, Karen M Moritz, and Mary E Wlodek

females. Regardless of maternal birth weight, F2 control and restricted male offspring had reduced whole-body insulin sensitivity and elevated plasma triglyceride concentrations, compared with female counterparts at 6 months. Furthermore, ageing to 12

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F.T.A. Fitzpatrick, M.D. Kendall, M.J. Wheeler, I.M. Adcock, and B.D. Greenstein

ABSTRACT

There was no visible thymus in ageing rats of 18 months, and 7 days after orchidectomy there was still no evidence of a thymus. By 30 days after the operation, however, there was a well-defined and well developed bilobular thymus overlying the heart, although it was smaller than those observed in 10-week-old rats. Histologically, the tissue appeared normal, was well vascularized, filled with lymphocytes and several mitotic figures were also seen. When compared with sham-operated animals, blood from these animals had a significantly higher lymphocyte count. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing.

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Y. S. Davidson, I. Davies, and C. Goddard

ABSTRACT

The mechanism of water conservation is impaired in ageing mammals. An age-related defect in the release of vasopressin has been implicated but, more recently, attention has moved to the renal component of the water conservation mechanism. Previous studies using renal cells prepared from mice of different ages have shown that the threshold dose of vasopressin required to elicit a significant rise in cyclic AMP (cAMP) was greater in older animals. The dose–response curve was moved to the right in 35-month-old mice, i.e. the concentration of vasopressin required to give maximum cAMP output was increased. To investigate this further we examined the binding of vasopressin to renal medullary cells maintained in short-term culture, to determine whether the decreased response of cAMP levels to vasopressin is due to changes in hormone-receptor interaction. In 6-month-old male mice the dissociation constant (K d) was 2·38 nmol/l and the maximum binding of the hormone (Bmax) was 47·6 fmol/106 cells, and at 30 months of age K d was 2·37 nmol/l and Bmax was 47·0 fmol/106 cells. In female mice the changes were more complicated because the data for the 6-month-old mice could be split into two groups. It is concluded that there are no age-related differences in the numbers of receptors or their affinity for vasopressin, and that the decreased cAMP response is probably associated with post-receptor mechanisms in this species.

J. Endocr. (1987) 115, 379–385

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G. D. GRAY

Department of Physiology, Stanford University School of Medicine, Stanford, California 94305, U.S.A.

(Received 26 September 1977)

Pituitary-testicular function changes substantially with increasing age in male rats; the levels of testosterone and gonadotrophins in the circulation are reduced in old animals (Ghanadian, Lewis & Chisholm, 1976; Riegle & Meites, 1976; Chan, Leathem & Esashi, 1977). However, previous studies compared only young and very old rats (more than 18 months) and the development of age-related changes in the concentrations of testosterone and gonadotrophins has not been examined. Since ageing is a complex interaction of physiological changes over a prolonged period of time, information on the precise timing of the various changes is important in establishing functional relationships in the ageing process. This study investigates hormonal changes in a group of male rats between 8 and 21 months old.

Adult male Long–Evans rats were housed three/cage in a temperature-controlled room with a 14

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E. D. ALBRECHT, R. D. KOOS, and W. B. WEHRENBERG

Biological Sciences Department, Purdue University, Fort Wayne, Indiana 46805, U.S.A.

(Received 1 December 1976)

A decline in rodent adrenal function with ageing has been suggested by reduced adrenal corticosterone production in vitro (Nandi, Bern, Biglieri & Pieprzyk, 1967) and corticosterone in the circulation (Grad & Khalid, 1968) of aged female mice, and adrenal Δ5-3β-hydroxysteroid dehydrogenase (3β-HSD) activity of aged female rats (Shapiro & Leathem, 1971). Other studies show no age-related decline in 'resting' plasma (Hess & Riegle, 1970) or adrenal (Sencar-Cupovic & Milkovic, 1976) corticosterone content in rats. Studies relating ageing and pituitary– adrenal function have also yielded apparently conflicting results. A reduced plasma corticosterone response to adrenocorticotrophin (ACTH) occurred in aged mice (Eleftheriou, 1974) and rats (Hess & Riegle, 1970), but plasma corticosterone levels after stress were similar in young and old rats (Sencar-Cupovic & Milkovic, 1976). Corticosteroid levels in the circulation, however, may inaccurately reflect adrenal function should

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M Novelli, V De Tata, M Bombara, A Lorenzini, M Masini, M Pollera, E Bergamini, and P Masiello

This study was aimed at exploring the capability of the pancreatic endocrine adaptive mechanisms of ageing Sprague-Dawley rats to counteract the metabolic challenge induced by the prolonged administration of dexamethasone (DEX) (0.13 mg/kg per day for 13 days). DEX treatment induced peripheral insulin resistance in 3-, 18- and 26-month-old rats, as indicated by the significant and persistent rise of plasma insulin levels in each age group (plasma insulin in 3-, 18- and 26-month-old rats from basal values of 4.3+/-0.8, 4.7+/-0.5 and 5.6+/-1.0 ng/ml (means+/-s.e.m.) respectively, rose to 11.9+/-1.7, 29.1+/-5.5 and 27.9+/-2.7 ng/ml respectively, after 9 days of administration). However, plasma glucose concentrations remained unchanged during the treatment in young rats, whereas they increased up to frankly diabetic levels in most 18-month-old and in all 26-month-old animals after a few days of DEX administration. Plasma free fatty acid concentrations increased 2-fold in 3- and 26-month-old rats and 4-fold in 18-month-old rats and could possibly be involved in the glucocorticoid-induced enhancement in insulin resistance, although they showed no significant correlation with glycaemic values. Incubation of pancreatic islets obtained from treated rats showed that DEX administration increased the insulin responsiveness of islets from not only younger but also older donors. However, in the islets of ageing rats, which already showed an age-dependent impairment of the sensitivity to glucose and other secretagogues, this enhancing effect was clearly attenuated with respect to the younger counterpart. Furthermore, DEX treatment depressed significantly the priming effect of glucose in islets isolated from all the three age groups. In conclusion, our results show that ageing rats are unable to counteract effectively a prolonged hyperglycaemic challenge as such induced by DEX administration. This homeostatic defect can be ascribed to the age-dependent failure of the endocrine pancreas to provide enough insulin to overcome the aggravation of an antecedent state of increased peripheral insulin resistance.

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C Fernandez-Galaz, T Fernandez-Agullo, F Campoy, C Arribas, N Gallardo, A Andres, M Ros, and JM Carrascosa

Leptin interacts with specific receptors in hypothalamic nuclei and modulates energy balance. Growing evidence has shown the association of obesity and hyperleptinaemia with non-insulin-dependent diabetes mellitus and insulin resistance. The aged Wistar rat shows peripheral insulin resistance in the absence of obesity and alterations of glucose homeostasis. However, it is not known whether, in these animals, the leptin action is altered. Here we studied the effect of ageing on plasma leptin concentration and the ability of hypothalamic nuclei to capture i.c.v.-injected digoxigenin-labelled leptin. Our data indicate that 24-month-old animals are hyperleptinaemic. However, daily food intake was greater in old animals, suggesting that they are leptin resistant. Leptin uptake in the hypothalamus was reduced in old rats. This uptake was a receptor-mediated process as demonstrated by displacement. Leptin accumulation in hypothalamic nuclei was partially colocalized with neuropeptide Y fibres. Immunohistochemical and western blot analyses showed a lower amount of the long form of leptin receptors in the hypothalamus of aged rats. Analysis by RT-PCR also demonstrated a decreased expression of leptin receptor mRNA in old animals. We conclude that the lower leptin uptake may be explained, at least in part, by a decreased amount of receptors in hypothalamic neurones of the aged rats.

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J. H. LEATHEM and N. M. APPEL

Bureau of Biological Research, Rutgers University, New Brunswick, New Jersey 08903, U.S.A.

(Received 24 March 1977)

Dehydrogenase enzyme activity linked to NADP has been implicated in the regulation of steroidogenesis in the adrenal gland and ovary (McKerns, 1964, 1965). Furthermore, glucose6-phosphate dehydrogenase (G6PD) activity increases after trophic hormone stimulation, suggesting a metabolic role in the stimulated cells (Castracane & Leathern, 1976). However, little consideration has been given to G6PD as a metabolic marker in steroidogenic organs in relation to ageing. Trout (1974) found G6PD activity to be greater in the adrenal glands of female than of male Wistar rats, but observed no change with age up to 19 months, whereas Stewart & Hunter (1969) recorded a decline in both adrenal and ovarian G6PD activity in 24-month-old Long-Evans rats. A re-examination of G6PD activity in the adrenal glands, testes and ovaries (which exhibit a decline in the formation of follicles: Leathem

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Mark E Cleasby, Pauline M Jamieson, and Philip J Atherton

Associations between obesity, diabetes and skeletal muscle ageing The International Diabetes Federation has estimated that there were 382 million people living with diabetes in 2013, with this number predicted to rise to 592 million by 2035

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B. D. GREENSTEIN

Available high-affinity binding sites for 5α-dihydrotestosterone (DHT) were measured in cytosols obtained from the amygdala, hypothalamus, anterior pituitary gland and ventral prostate gland of 12-week-old rats at various times after orchidectomy, and in the corresponding tissues of 18-month-old male rats. It is suggested that the lower affinity of the DHT binding reaction in brain and ventral prostatic cytosols after orchidectomy or ageing respectively, may explain, at least in part, the changes in the responsiveness of the tissues to androgens.