Age-Dependent and Gender-Dependent Regulation of Hypothalamic-Adrenocorticotropic-Adrenal Axis

Veldhuis, Johannes D.; Sharma, Animesh; Roelfsema, Ferdinand

doi:10.1016/j.ecl.2013.02.002

Cited by 95 publications

(86 citation statements)

References 237 publications

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“…There is, however, some evidence to suggest diminished negative feedback on cortisol production, which may lead to a greater response to corticotropin-releasing hormone (CRH) challenge, particularly in women [26]. Similarly, the mineralocorticosteroid aldosterone demonstrates a moderate decrease during life, and both this and an associated decrease in plasma renin activity are considered to impact minimally on physiological processes in the elderly [35,36]. …”

Section: The Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

“…Unlike many other hormones, concentrations of both cortisol and its binding globulin remain relatively consistent throughout ageing [35,36]. There is, however, some evidence to suggest diminished negative feedback on cortisol production, which may lead to a greater response to corticotropin-releasing hormone (CRH) challenge, particularly in women [26].…”

Section: The Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

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The Endocrinology of Ageing: A Mini-Review

Jones

Boelaert

2014

Gerontology

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Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related morbidities. Complex alterations in hormonal networks which regulate homeostasis and survival may underlie this poor adaptation to later life, as exemplified by an increased fracture risk amongst post-menopausal women. Beyond overt under- or overactivity of hormonal axes, changes in the concentrations of regulatory hormones may also impact on health and disease. Subclinical hyperthyroidism, a disorder characterised by normal thyroxine levels in the presence of decreased thyroid-stimulating hormone, is, for instance, independently associated with an increased risk of atrial fibrillation amongst elderly populations. Both the menopause and subclinical thyroid disease demonstrate the difficulty in reversing endocrine changes in later life, with minimal impact from thyroxine therapy in subclinical hypothyroidism and multiple reports of harm resulting from hormone replacement therapy in peri- and post-menopausal women. Given these findings, strategies to locally regulate hormone bioavailability by altering pre-receptor metabolism may offer greater therapeutic potential in the fight against age-related disease. This review aims to provide an overview of the ageing endocrine system and its potential impact on health and disease in the elderly. It will postulate that strategies to coordinate pre-receptor hormone metabolism and a greater understanding of putative hormonal longevity pathways may offer key new drug targets in the fight against ageing, and will argue against applying the conventional endocrine maxim of ‘block and replace' to hormonal changes seen during ageing.

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Section: The Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

Section: The Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

The Endocrinology of Ageing: A Mini-Review

Jones

Boelaert

2014

Gerontology

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“…Older individuals were studied since sex differences in ACTH responses may be greater and/or more consistent in older than young humans (reviewed in Ref. 37). The hypothesis was that the short-term sex-steroid milieu, rather than gender per se, governs cortisol-dependent negative feedback on mean, pulsatile, and entropic ACTH secretion in healthy men and women.…”

mentioning

confidence: 99%

Estradiol, but not testosterone, heightens cortisol-mediated negative feedback on pulsatile ACTH secretion and ACTH approximate entropy in unstressed older men and women

Sharma

Aoun

Wigham

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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How sex steroids modulate glucocorticoid feedback on the hypothalamic-pituitary-corticotrope (HPC) unit is controversial in humans. We postulated that testosterone (T) in men and estradiol (E2) in women govern unstressed cortisol-mediated negative feedback on ACTH secretion. To test this hypothesis, 24 men and 24 women age 58 ± 2.4 yr were pretreated with leuprolide and either sex steroid (E2 in women, T in men) or placebo addback. Placebo or ketoconazole (KTCZ) was administered overnight to inhibit adrenal steroidogenesis during overnight 14-h intravenous infusions of saline or cortisol in a continuous versus pulsatile manner to test for feedback differences. ACTH was measured every 10 min during the last 8 h of the infusions. The main outcome measures were mean ACTH concentrations, pulsatile ACTH secretion, and ACTH approximate entropy (ApEn). ACTH concentrations were lower in women than men (P < 0.01), and in women in the E2+ compared with E2- group under both continuous (P = 0.01) and pulsatile (P = 0.006) cortisol feedback, despite higher cortisol binding globulin and lower free cortisol levels in women than men (P < 0.01). In the combined groups, under both modes of cortisol addback, ACTH concentrations, pulsatile ACTH secretion, and ACTH secretory-burst mass correlated negatively and univariately with E2 levels (each P < 0.005). E2 also suppressed ACTH ApEn (process randomness) during continuous cortisol feedback (P = 0.004). T had no univariate effect but was a positive correlate of ACTH when assessed jointly with E2 (negative) under cortisol pulses. In conclusion, sex steroids modulate selective gender-related hypothalamic-pituitary adrenal-axis adaptations to cortisol feedback in unstressed humans.

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“…Furthermore, this increased HPA activation in postmenopausal women is blunted by estradiol replacement [88,89]. In animal models sex differences in response to stress and ACTH release have been well documented [90][91][92][93].…”

Section: Stress the Brain And Hypertensionmentioning

confidence: 95%

Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors

Hay

2015

Clinical Science

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Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension.

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Age-Dependent and Gender-Dependent Regulation of Hypothalamic-Adrenocorticotropic-Adrenal Axis

Cited by 95 publications

References 237 publications

The Endocrinology of Ageing: A Mini-Review

The Endocrinology of Ageing: A Mini-Review

Estradiol, but not testosterone, heightens cortisol-mediated negative feedback on pulsatile ACTH secretion and ACTH approximate entropy in unstressed older men and women

Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors

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