Corticosteroid receptors and aging (original) (raw)
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Age-Related Changes in Glucocorticoid Fast Feedback Inhibition of Adrenocorticotropin in Man1
The Journal of Clinical Endocrinology and Metabolism, 1998
A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid feedback suppression seems to occur with aging. To investigate possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg as an iv bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr) men. Blood samples for ACTH and cortisol determinations were collected at Ϫ15, 0, 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both groups. In old men, in concomitance with the cortisol increase, ACTH levels showed only a slight and nonsignificant decrease within the first 15 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, followed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and young men, whereas the remaining part of the curve (from 60-180 min) showed no differences between the two groups. The slower response in glucocorticoid feedback inhibition of ACTH in old men supports the concept of some alteration in the central regulation by steroids in aging. Age-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnormalities could be involved in the fast component of hypothalamic-pituitaryadrenal axis feedback regulation.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2003
In aged humans, diminished mineralocorticoid receptor (MR)-mediated feedback in the brain could contribute to impaired feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis, but no study specifically compared young and old individuals with regard to MR function. We examined 10 healthy young (mean age +/- SD [standard deviation] 26.1 +/- 2.9 years) and 10 elderly men (68.3 +/- 4.7 years) at the nadir of cortisol levels (2:00 pm-9:00 pm) when HPA activity is mainly controlled by the MR. After pretreatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion, participants received orally, in randomized order on two separate occasions, either 0.5 mg of the MR agonist fludrocortisone or placebo. Fludrocortisone significantly decreased maximum adrenocorticotropic hormone (ACTH) and cortisol concentrations in both groups. ACTH and cortisol values after fludrocortisone were significantly higher in older men compared with young men. Our results implicate that a decrease in MR-mediated negative feedback contributes to the diminished feedback activity in older humans.
The Journals of Gerontology: Series A, 2020
Background The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress. Method We performed a standard 250 µg ACTH stimulation test in a home-based substudy of 51 women aged 85–96 years enrolled in the Women’s Health and Aging Study II who were not taking corticosteroids. We examined the cortisol and dehydroepiandrosterone (DHEA) responses at 0, 30, 60, and 120 minutes, overall and by frailty status. Results The peak cortisol response to ACTH could not be determined, with the highest levels at the 120-minute time point. Pre- and post-ACTH stimulated cortisol levels did not differ by frailty status over this time frame, with no difference in the characteristics of the dose-response curves. Pre- and post-ACTH stimulated DHEA levels also did not differ by frailty status, though the dose-response curves suggested divergence after stimulation, with a more rapid DHEA response with increasing f...
Glucocorticoid receptors in ageing rats
Experimental Gerontology, 1999
The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH.
Hormonal status of cortisol and dehydroepiandrosterone sulfate in an elderly Tunisian population
Comptes Rendus Biologies, 2007
Adrenal function and aging have been the object of intense interest recently, especially as regards dehydroepiandrosterone sulfate (DHEA-S), which is of major importance, since it is distinct from cortisol and aldosterone in declining with age. In a group of healthy old Tunisians, we investigated the association between cortisol and DHEA-S, on the one hand, and age, sex, lifestyle, physical health, including the body mass index (BMI), physical activity, and smoking indicators, on the other hand. We observed that cortisol concentrations did not change with aging, while DHEA-S concentrations decrease with age in both sexes. Cortisol/DHEA-S ratio, however, increases with aging. Our results revealed that DHEA-S levels are affected neither by physical activity nor by weight. It appears also that current smoking could not affect the level of DHEA-S. Relationships were found between DHEA-S concentrations and BMI, then between DHEA-S levels and serum cholesterol, triglycerides and calcium. No modification in the morning serum cortisol was found to be associated with aging. Decrease in DHEA-S levels is, however, clearly associated with this phenomenon. High cortisol/DHEA-S ratio accelerates the occurrence of some adult diseases, such as diabetes mellitus, atherosclerosis, dementia, and osteoporosis. Generally, the adrenal insufficiency marked by a cognitive impairment, immune disorders, sexual dysfunction, and scores for depression and anxiety can be corrected by a replacement of deficient DHEA-S.
Adrenal Aging and Its Implications on Stress Responsiveness in Humans
Frontiers in Endocrinology
Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, and diabetes, among others. In contrast to the increase in glucocorticoid levels, other adrenocortical hormones, particularly serum aldosterone and DHEA (the precursor to androgens and estrogens) show significant decreases in the elderly. The underlying mechanisms for their decrease remain unclear. While the adrenomedullary hormone, norephinephrine, shows an increase in plasma levels, associated with a decrease in clearance, no notable changes observed in plasma epinephrine levels in the elderly. The multiplicity and complexity of the adrenal hormone changes observed throughout the normal aging process, suggests that age-related alterations in cellular growth, differentiation, and senescence specific to the adrenal gland must also be considered.
The Journal of Clinical Endocrinology & Metabolism, 2000
We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal androgen deficiency in elderly women. To this end, we quantified basal morning concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and androstenedione (A4) and then evaluated the effects of overnight dexamethasone (DEX) suppression followed by adrenal responses to graded hourly infusions of ACTH, ranging from 20-1280 ng/1.5 m 2 ⅐h. Finally, we performed a standard 0.25-mg ACTH bolus stimulation test, with sampling at 1 h thereafter. Basal serum levels of DHEA, DS, and A4 were significantly reduced (ϳ50% each) in a group of 35 healthy postmenopausal women, 55-68 yr old, compared to those in 30 healthy, regularly menstruating women, 20-25 yr old. Post-DEX levels of these C 19 steroids also were significantly lower in the older women than in the younger women; the percent decrease after DEX for A4 was greater in the older women, whereas those in DHEA and DS were not age related. Basal and post-DEX levels of F were similar in both groups. Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate. The