Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline G.; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia Marques

doi:10.1016/j.jsbmb.2016.11.014

Cited by 9 publications

(7 citation statements)

References 55 publications

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“…However, whatever neuroprotection DHEA may afford most likely varies depending on the specific brain region involved, the developmental stage of the child and the sex‐specific effects of cortisol on the CNS. Indeed, although animal models showed a sexually dimorphic effect of DHEA on glucose uptake and oxidation in the cerebral cortex and hippocampus, there is no evidence of such sexually dimorphic effects of DHEA in humans, and brain‐hormone studies have shown no sex differences in the impact of DHEA on cortical thickness, cortico‐amygdalar or cortico‐hippocampal networks. On the other hand, there is well‐documented evidence of a sex difference in the density and distribution of glucocorticoid receptors in the human brain, as well as sex differences in neural circuits responding to corticotrophin signalling .…”

Section: Discussionmentioning

confidence: 99%

“…There is prior evidence of sexual dimorphisms in hypothalamic‐pituitary‐adrenal axis regulation in both animals and humans . In addition, DHEA was shown to regulate the main source of energy for the brain, glucose uptake, as well as glucose oxidation, in a sex‐dependent manner, and the process of adrenarche (with its increased production of adrenal steroids such as DHEA and cortisol) begins earlier in girls vs boys …”

Section: Introductionmentioning

confidence: 99%

“…Thus, hormonal states, brain structure and cognitive function all display sexual dimorphisms . Although some of these differences may be attributed to sex chromosomes, there is also evidence suggesting causal pathways linking brain‐hormone and cognitive development.…”

Section: Introductionmentioning

confidence: 99%

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Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Farooqi

Scotti

et al. 2019

J Neuroendocrinology

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Although dehydroepiandrosterone (DHEA) may exert neuroprotective effects in the developing brain, prolonged or excessive elevations in cortisol may exert neurotoxic effects. The ratio between DHEA and cortisol (DC ratio) has been linked to internalising and externalising disorders, as well as cognitive performance, supporting the clinical relevance of this hormonal ratio during development. However, the brain mechanisms by which these effects may be mediated have not yet been identified.Furthermore, although there is evidence that the effects of cortisol in the central nervous system may be sexually dimorphic in humans, the opposite is true for DHEA, with human studies showing no sex-specific associations in cortical thickness, cortico-amygdalar or cortico-hippocampal structural covariance. Therefore, it remains unclear whether sex moderates the developmental associations between DC ratio, brain structure, cognition and behaviour. In the present study, we examined the associations between DC ratio, structural covariance of the hippocampus with

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Farooqi

Scotti

et al. 2019

J Neuroendocrinology

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“…DHEA may also alter in a sex-specific way the glucose metabolism in the CNS. Thus, this neuroactive steroid decreases glucose uptake and increases glycogen content in cerebral cortex and olfactory bulb of male, but not of female animals (Vieira-Marques et al, 2017). In hypoglicemic animals, ERα and ERβ enhance astrocyte AMPK and glycogen synthase expression together with an inhibition of glycogen phosphorylase in female animals, while activation of ERβ suppresses these proteins in male animals (Hasan Mahmood et al, 2018).…”

Section: Diabetic Encephalopathymentioning

confidence: 95%

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Giatti

Diviccaro

Serafini

et al. 2020

Frontiers in Neuroendocrinology

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The nervous system, in addition to be a target for steroid hormones, is the source of a variety of neuroactive steroids, which are synthesized and metabolized by neurons and glial cells. Recent evidence indicates that the expression of neurosteroidogenic proteins and enzymes and the levels of neuroactive steroids are different in the nervous system of males and females. We here summarized the state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules. In addition, we discuss the consequences of sex differences in neurosteroidogenesis for the function of the nervous system under healthy and pathological conditions and the implications of neuroactive steroids and neurosteroidogenesis for the development of sex-specific therapeutic interventions.

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“…In the last several decades, several studies explored the relationship between DHEA and neurodegenerative diseases [78][79][80]. It was found that age-dependent DHEA reduction can cause a series of age-related degenerative diseases, including Alzheimer's disease and Parkinson disease [81,82], and DHEA as a sigma-1 receptor ligand became a therapeutic candidate in degenerative diseases [44,83].…”

Section: Supplementation With Dhea May Improve the Pregnancy Outcome mentioning

confidence: 99%

Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

Jiang

Cui

Zhang

et al. 2020

Aging

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Sigma non-opioid intracellular receptor 1 (sigma-1 receptor), a non-opioid transmembrane protein, is located on cellular mitochondrial membranes and endoplasmic reticulum. Current research has demonstrated that sigma-1 receptor is related to human degenerative diseases. This study is focused on the effects of sigma-1 receptor on the pathophysiological process of diminished ovarian reserve (DOR) and granulosa cells (GCs) apoptosis. Sigma-1 receptor concentration in follicular fluid (FF) and serum were negatively correlated with basal follicle-stimulating hormone (FSH) and positively correlated with anti-mullerian hormone (AMH), antral follicle count (AFC). Sigma-1 receptor reduction in GCs was accompanied by endoplasmic reticulum stress (ERS)-mediated apoptosis in women with DOR. Plasmid transfection was used to establish SIGMAR1-overexpressed and SIGMAR1-knockdown human granulosa-like tumor (KGN) cell and thapsigargin (TG) was used to induce ERS KGN cells. We found that KGN cells treated with endogenous sigma-1 receptor ligand dehydroepiandrosterone (DHEA) and sigma-1 receptor agonist PRE-084 showed similar biological effects to SIGMAR1-overexpressed KGN cells and opposite effects to SIGMAR1knockdown KGN cells. DHEA may improve DOR patients' pregnancy outcomes by upregulating sigma-1 receptor and downregulating ERS-mediated apoptotic genes in GCs. Thus, sigma-1 receptor may be a potential ovarian reserve biomarker, and ligand-mediated sigma-1 receptor activation could be a future approach for DOR therapy.

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Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS

Cited by 9 publications

References 55 publications

Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

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