DHEA: A Biologist's Perspective

Hornsby, Peter J.

doi:10.1111/j.1532-5415.1997.tb02941.x

Cited by 40 publications

(18 citation statements)

References 96 publications

(103 reference statements)

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“…DHEA and DHEAS, which are collectively designated DHEA(S), are secreted in high amounts in humans and a few other primates. The highest reported plasma concentration of DHEA(S) in humans is about 10 M (Parker and Odell, 1980;Guillemette et al, 1996;Hornsby, 1997), which is close to our EC 50 value (6.7 M) for DHEA effect on the capsaicin response (Fig. 1B).…”

Section: Discussionsupporting

confidence: 71%

Competitive Inhibition of the Capsaicin Receptor-Mediated Current by Dehydroepiandrosterone in Rat Dorsal Root Ganglion Neurons

Chen

Chang²,

Wu³

2004

J Pharmacol Exp Ther

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The effects of dehydroepiandrosterone (5-androsten-3␤-ol-17-one; DHEA) and related steroids on the capsaicin receptormediated current were studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique. DHEA rapidly and reversibly inhibited the capsaicininduced current in a concentration-dependent manner, with an EC 50 of 6.7 M and a maximal inhibition of 100%. DHEA increased the capsaicin EC 50 with little effect on the capsaicin maximal response, suggesting that the blocking action of DHEA is competitive. Neither the capsaicin response nor inhibition of the capsaicin response by extracellularly applied DHEA was significantly affected by inclusion of a saturating concentration of DHEA in the electrode buffer, arguing that DHEA acted at the extracellular surface of the membrane. Moreover, DHEA did not act through protein phosphatases to inhibit the capsaicin-induced current. Furthermore, the stereoisomer of DHEA, 5-androsten-3␣-ol-17-one, failed to inhibit the capsaicin-induced current, producing instead a potentiating effect on the capsaicin response, demonstrating that the interaction of steroids with the capsaicin receptor is stereospecific. The inhibitory action of DHEA on the capsaicin-induced current may provide a basis for reducing capsaicin receptor-mediated nociception.

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Section: Discussionsupporting

confidence: 71%

Competitive Inhibition of the Capsaicin Receptor-Mediated Current by Dehydroepiandrosterone in Rat Dorsal Root Ganglion Neurons

Chen

Chang²,

Wu³

2004

J Pharmacol Exp Ther

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“…Only in humans and a few primates do the adrenals secrete dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) (69,70); in particular, the zona reticularis of the adrenal cortex is the exclusive source for DHEA and DHEAS, and the level of expression of 3b-hydroxysteroid dehydrogenase is the most important determinant for their biosynthesis (71).…”

Section: Dehydroepiandrosterone Sulfate (Dheas) and Agingmentioning

confidence: 99%

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates

Ferrari

Cravello

Muzzoni

et al. 2001

European Journal of Endocrinology

246

156

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The aim of this review was to examine the evidence for age-related changes of the hypothalamic± pituitary±adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings.A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people.The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls.Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.

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“…DHEA may be a reliable biomarker of aging specifically in men (Roth et al, 2002) and a potential predictor of mortality (Mazat et al, 2001). Hornsby (1997) makes the case that the most likely function for DHEA is as a precursor for conversion to potent androgens, which mediate adrenarchy, a sexual signaling mechanism occurring just before puberty in higher primates. The shrinkage of the DHEA-secreting tissue zone of the adrenal cortex and the decrease in DHEA levels could be considered as the post-pubertal involution of an organ whose function has been fulfilled and is no longer necessary, rather than as a phenomenon of aging or senescence.…”

Section: Dehydroepiandrosteronementioning

confidence: 99%

“…However, DHEA has been demonstrated to behave both as an antioxidant and a prooxidant, depending on the conditions of the experiment (Mooradian, 1993;Gallo et al, 1999). Both in vitro and in vivo, DHEA has been shown to protect against lipid peroxidation, cell death and toxicities induced by H 2 O 2 , carbon tetrachloride, copper, and hyperglycemia (Gallo et al, 1999;Bastianetto et al, 1999;Whitcomb and Schwartz, 1985;Rom and Harkin, 1991;Brignardello et al, 2000;Boccuzzi et al, 1997;Aragno et al, 1993;1997). In rats subjected to repeated immobilization stress, DHEA administration partly reversed stressinduced inhibition of body weight gain, increases in adrenal weight and glucocorticoid receptor levels, and decreased lipid peroxidation, suggesting that DHEA may act an anti-stress hormone by reducing free radical generation (Hu et al, 2000).…”

Section: Dehydroepiandrosteronementioning

confidence: 99%

Hormonal regulation of longevity in mammals

Brown‐Borg

2007

Ageing Research Reviews

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Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant.

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DHEA: A Biologist's Perspective

Cited by 40 publications

References 96 publications

Competitive Inhibition of the Capsaicin Receptor-Mediated Current by Dehydroepiandrosterone in Rat Dorsal Root Ganglion Neurons

Competitive Inhibition of the Capsaicin Receptor-Mediated Current by Dehydroepiandrosterone in Rat Dorsal Root Ganglion Neurons

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates

Hormonal regulation of longevity in mammals

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