Photo-DHEA—A functional photoreactive dehydroepiandrosterone (DHEA) analog

Waschatko, Gustav; Kojro, Elżbieta; Zahnow, Michael; Gehrig‐Burger, Katja

doi:10.1016/j.steroids.2011.01.009

Cited by 6 publications

(3 citation statements)

References 25 publications

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“…DHEA (100 nM for 24 h) inhibited serum deprivation-induced apoptosis in DU145 prostate and Caco2 colorectal carcinoma cells in a TRKA-and p75NTR-specific manner (Anagnostopoulou et al 2013). Another group synthesized a photoreactive DHEA analog, showed that it is specifically bound to the PM of PC12 cells, and activated adenylyl cyclase to increase cAMP in HepG2 human hepatoma cells (Waschatko et al 2011).…”

Section: Dhea Action In Neuronal/cns Cellsmentioning

confidence: 99%

Novel mechanisms for DHEA action

Prough

Clark

Klinge

2016

Journal of Molecular Endocrinology

128

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Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, and its sulfated metabolite DHEA-S are the most abundant endogeneous circulating steroid hormones. DHEA actions are classically associated with age-related changes in cardiovascular tissues, female fertility, metabolism, and neuronal/CNS functions. Early work on DHEA action focused on the metabolism to more potent sex hormones, testosterone and estradiol, and the subsequent effect on the activation of the androgen and estrogen steroid receptors. However, it is now clear that DHEA and DHEA-S act directly as ligands for many hepatic nuclear receptors and G-protein-coupled receptors. In addition, it can function to mediate acute cell signaling pathways. This review summarizes the molecular mechanisms by which DHEA acts in cells and animal models with a focus on the 'novel' and physiological modes of DHEA action.

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Section: Dhea Action In Neuronal/cns Cellsmentioning

confidence: 99%

Novel mechanisms for DHEA action

Prough

Clark

Klinge

2016

Journal of Molecular Endocrinology

128

View full text Add to dashboard Cite

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“…Dehydroepiandrosterone (DHEA) is a human antistress 19-carbon steroid hormone [7], secreted mainly by the adrenal glands [8]. Most DHEA is secreted in the form of dehydroepiandrosterone-sulfate (DHEA-S) into the circulatory system [9] and converted to either androgens or estrogens [10–12].…”

Section: Introductionmentioning

confidence: 99%

“…Reports in the literature claim that CYP2C9 metabolizes DHEA-S, thus creating a reduced level of circulating DHEA in elderly people and, consequentially, causing aging and lowered disease resistance [15, 16]. Therefore it would seem that the inhibition of CYP2C9 can increase the level of DHEA in the circulatory system and reduce geriatric problems [7, 8, 17, 18]. …”

Section: Introductionmentioning

confidence: 99%

In SilicoInvestigation of Cytochrome P450 2C9 in relation to Aging Using Traditional Chinese Medicine

Hung

Kuo

Chen

2014

Evidence-Based Complementary and Alternative Medicine

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Cytochrome P450 2C9 (CYP2C9) metabolizes dehydroepiandrosterone-sulfate (DHEA-S), but in elderly people the amount of DHEA-S remaining after CYP2C9 metabolization may be insufficient for optimal health. A prediction model, molecular docking, and molecular dynamics were used to screen the Traditional Chinese Medicine (TCM) database to determine molecular compounds that may inhibit CYP2C9. The candidate compounds apocynoside(I), 4-methoxymagndialdehyde, and prunasin have higher Dock Scores, and prediction bioactivity than warfarin (the control drug). The interaction between 4-methoxymagndialdehyde and CYP2C9 is more intense than with other TCM compounds, but the simulation is longer. In these compounds, apocynoside(I) and prunasin have a greater number of pathways for their flexible structure, but these structures create weak interactions. These candidate compounds, which are known to have antioxidation and hypolipidemic functions that have an indirect effect on the aging process, can be extracted from traditional Chinese medicines. Thus, these candidate compounds may become CYP2C9 inhibitors and play an important role in providing optimal health in the elderly.

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Dehydroepiandrosterone (DHEA): Hypes and Hopes

Rutkowski

Sowa

Rutkowska-Talipska

et al. 2014

Drugs

159

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Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a 'superhormone' and an 'anti-aging' panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25(hi) and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.

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Photo-DHEA—A functional photoreactive dehydroepiandrosterone (DHEA) analog

Cited by 6 publications

References 25 publications

Novel mechanisms for DHEA action

Novel mechanisms for DHEA action

In SilicoInvestigation of Cytochrome P450 2C9 in relation to Aging Using Traditional Chinese Medicine

Dehydroepiandrosterone (DHEA): Hypes and Hopes

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