Corticosteroid receptors and aging

Armanini, Decio; Scali, M.; Vittadello, Gabriele; Ribecco, M.; Zampollo, V.; Pratesi, C.; Orlandini, Elisa; Zovato, Stefania; Zennaro, Maria-Christina; Karbowiak, I.

doi:10.1016/0960-0760(93)90141-i

Cited by 18 publications

(14 citation statements)

References 17 publications

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“…However, conflicting results on the basal level of receptors during aging, obtained in studies performed on various animal tissues have been published. Numerous authors reported decrease of GR number during aging in human and rodent tissues (Roth and Hess 1982;Sharma and Timiras 1987a;Tanaka et al 1991;Armanini et al 1993;Hirano et al 1997). On the other hand there are various reports indicating that in rodent liver concentration of GR did not reduce significantly with aging (Roth 1974;Bolla 1980).…”

Section: Discussionmentioning

confidence: 94%

“…An increased amount of published data indicates that normal processes of aging are result of changes in level of steroid receptors (Roth and Hess 1982;Armanini et al 1993;Ranhotra and Sharma 2001) that reflect through changes in synthesis and activity of metabolic enzymes (Singer and Litwack 1971;Kanungo 1980;Djordjevic-Markovic et al 1999). However, conflicting results on the basal level of receptors during aging, obtained in studies performed on various animal tissues have been published.…”

Section: Discussionmentioning

confidence: 96%

“…In spite of reported data on reduced GR signaling in liver of aged animals (Roth and Hess 1982;Armanini et al 1993;Ranhotra and Sharma 2001), the data describing the state of GR in liver tissue at more than two phases during the age of rats are still lacking. Accordingly, the aim of this study was to examine the effects of age and glucocorticoids on GR and enzyme activity in liver tissue of rats at five time points of age.…”

Section: Introductionmentioning

confidence: 82%

“…It has been also reported that GR reduction is occurred with increased plasma cortisol concentration in aged subject (Armanini 1993), as well as that the basal level of GR is decreased in old rats (Roth and Hess 1982;Armanini et al 1993). Namely, an increased amount of data in literature indicates that normal processes of aging are result of changes in steroid receptor levels in the appropriate target cells both in animals and humans (Roth 1979;Armanini et al 1993;Nichols 1998;Ranhotra and Sharma 2001). Responsiveness to certain hormone at the cellular level is also reported to decrease with age (Roth 1979).…”

Section: Introductionmentioning

confidence: 88%

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Basal and glucocorticoid induced changes of hepatic glucocorticoid receptor during aging: relation to activities of tyrosine aminotransferase and tryptophan oxygenase

Ribarac-Stepic¹,

Vulovic²,

Korićanac³

et al. 2005

Biogerontology

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The characteristics of glucocorticoid receptors, their sensitivity to glucocorticoid as well as the basal and glucocorticoid induced thyrosine aminotranferase (TAT) and tryptophan oxygenase (TO) activities were studied in rat liver during aging. The concentration (N) and dissociation constant (K(d)) of glucocorticoid receptor (GR) significantly change during the aging both in untreated and dexamethasone treated animals. The level of receptors was lower in dexamethasone treated rats of all analyzed aged groups compared to untreated animals. In comparison to untreated groups, there was no correlation between the changes of N and K(d) during the lifespan. According to immunochemical analysis, the decline of receptor protein content occurs during lifespan. Dexamethasone treatment reduced the level of receptor protein compare to respective age group of untreated rats. The glucocorticoid-receptor (G-R) complexes from both untreated and treated animals underwent thermal activation, although the extent of activation was more pronounced in the case of untreated groups compared to treated animals. The magnitude of heat activation of receptor complexes was more pronounced in the liver of the youngest untreated rats compared to elderly ones, while the receptor activation between treated groups of studied ages has shown less significant differences. Besides, basal as well as induced TAT and TO activities after dexamethasone injection also showed age-related alterations. The observed alterations in GR might play a role in the changes of the cell responses to glucocorticoid during the age. This presumption is supported by detected changes in basal and dexamethasone induced TAT and TO activities during aging.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 88%

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Basal and glucocorticoid induced changes of hepatic glucocorticoid receptor during aging: relation to activities of tyrosine aminotransferase and tryptophan oxygenase

Ribarac-Stepic¹,

Vulovic²,

Korićanac³

et al. 2005

Biogerontology

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“…This finding may be due to the development of resistance to glucocorticoid action in many ICU patients due to inflammatory cytokine action [37][38][39]. Elderly patients may have more resistance to glucocorticoid action than younger patients as glucocorticoid resistance has also been reported to be a concomitant of normal aging in peripheral mononuclear cells [40]. The trend to a higher baseline serum cortisol and the smaller response to ACTH stimulation seen in this study may indicate that in elderly critically ill patients the adrenal glands are functioning near maximally due to end-organ resistance output and have limited adrenal reserve in the face of further stimulation.…”

Section: Discussionmentioning

confidence: 99%

Changes in Serum Cortisol with Age in Critically Ill Patients

Beale¹,

Zhu²,

Belzberg³

2002

Gerontology

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Background: Mortality in the intensive care unit (ICU) rises with age, a high basal serum cortisol and a small response to adrenocorticotropin (ACTH) stimulation. Even slight impairment of the adrenal response during severe illness can be lethal. Objectives: To determine if age is associated with changes in basal or stimulated serum cortisol in critically ill patients. Methods: We studied 2 groups of surgical ICU patients with hypotension despite ≧6 h of catecholamine therapy. Group 1 comprised 7 patients aged <30 (mean 22.9 ± 3.7) years, and group 2 comprised 8 patients aged >60 (mean 75.8 ± 10.3) years (p < 0.001). We compared baseline serum cortisol levels and the serum cortisol response 30 and 60 min after stimulation with low-dose (1 µg) and 2 h later standard-dose (250 µg) ACTH. We also determined the incidence of adrenal insufficiency in each group using standard criteria and compared selected clinical variables. Results: There was no significant difference in the mean serum cortisol at baseline although it tended to be higher in older patients. Group 2 patients had a significantly smaller response to the low-dose test at 30 min (p = 0.002), and to the standard-dose test at both 30 (p = 0.02) and 60 min (p = 0.04). There was no significant difference in the incidence of adrenal insufficiency between the 2 groups: 1/7 or 14.3% in group 1 vs. 1/8 or 12.5% in group 2 (p = 1.0). There was no significant difference between the 2 groups in the mean acute physiology score, blood pressure, serum albumin, dopamine, or dobutamine dose (p > 0.05). Creatinine clearance was significantly lower in group 2 (p > 0.001) and endogenous ACTH significantly higher (p = 0.04). Significantly more patients in group 1 (5/7, 72%) than group 2 (1/8, 12.5%) had a diagnosis of trauma on admission (p = 0.04). Seven of the eight patients (88%) in group 2 vs. 1/7 (14%) of patients in group 1 died in the ICU, but this difference was not statistically significant (p = 0.18). Conclusion: In this small exploratory study, baseline serum cortisol tended to be higher in older patients and older patients had a significantly smaller response to ACTH stimulation on both low-dose and standard-dose tests. In view of the high death rate in the older ICU patients, the findings in this study need to be confirmed in a larger study. The mechanism and clinical significance of these findings remain to be determined but may be related to deterioration in renal function with age.

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