Mechanisms of Action of Dehydroepiandrosterone

Vitamins and Hormones
Barbara J ClarkCarolyn M Klinge

Abstract

Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA) and its sulfated metabolite DHEA-S are the most abundant steroids in circulation and decline with age. Rodent studies have shown that DHEA has a wide variety of effects on liver, kidney, adipose, reproductive tissues, and central nervous system/neuronal function. The mechanisms by which DHEA and DHEA-S impart their physiological effects may be direct actions on plasma membrane receptors, including a DHEA-specific, G-protein-coupled receptor in endothelial cells; various neuroreceptors, e.g., aminobutyric-acid-type A, N-methyl-d-aspartate (NMDA), and sigma-1 (S1R) receptors; by binding steroid receptors: androgen and estrogen receptors (ARs, ERα, or ERβ); or by their metabolism to more potent sex steroid hormones, e.g., testosterone, dihydrotestosterone, and estradiol, which bind with higher affinity to ARs and ERs. DHEA inhibits voltage-gated T-type calcium channels. DHEA activates peroxisome proliferator-activated receptor (PPARα) and CAR by a mechanism apparently involving PP2A, a protein phosphatase dephosphorylating PPARα and CAR to activate their transcriptional activity. We review our recent study showing DHEA activated GPER1 (G-protein-coupled estrogen receptor...Continue Reading

Citations

May 23, 2020·Journal of Applied Animal Welfare Science : JAAWS·M PlacciPier Attilio Accorsi
Mar 19, 2020·Current Alzheimer Research·Dubravka S StracNela Pivac
Sep 16, 2020·Journal of Neuroscience Research·Clayton PeixotoAndré Barciela Veras
Mar 21, 2020·Frontiers in Endocrinology·Benjamin Campbell
Mar 8, 2021·Molecular and Cellular Endocrinology·Typhanie Dumontet, Antoine Martinez
Nov 12, 2021·Bioscience Trends·Siwei ZhangLing Wang

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