Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Dehydroepiandrosterone (DHEA): Pharmacological Effects and Potential Therapeutic Application

Author(s): Nemanja Nenezic, Smiljana Kostic, Dubravka Svob Strac, Marija Grunauer, Dragana Nenezic, Milica Radosavljevic, Jasna Jancic and Janko Samardzic*

Volume 23, Issue 8, 2023

Published on: 20 October, 2022

Page: [941 - 952] Pages: 12

DOI: 10.2174/1389557522666220919125817

Abstract

Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of growth and decline of its synthesis during life was observed, together with the corresponding formation of its sulphate ester (DHEAS). High levels of plasma circulating DHEA are suggested as a marker of human longevity, and various pathophysiological conditions lead to a decreased DHEA level, including adrenal insufficiency, severe systemic diseases, acute stress, and anorexia. More recent studies have established the importance of DHEA in the central nervous system (CNS). A specific intranuclear receptor for DHEA has not yet been identified; however, highly specific membrane receptors have been detected in endothelial cells, the heart, kidney, liver, and the brain. Research shows that DHEA and DHEAS, as well as their metabolites, have a wide range of effects on numerous organs and organ systems, which places them in the group of potential pharmacological agents useful in various clinical entities. Their action as neurosteroids is especially interesting due to potential neuroprotective, pro-cognitive, anxiolytic, and antidepressant effects. Evidence from clinical studies supports the use of DHEA in hypoadrenal individuals and in treating depression and associated cognitive disorders. However, there is also an increasing trend of recreational DHEA misuse in healthy people, as it is classified as a dietary supplement in some countries. This article aims to provide a critical review regarding the biological and pharmacological effects of DHEA, its mechanism of action, and potential therapeutic use, especially in CNS disorders.

Keywords: Dehydroepiandrosterone, biosynthesis, pharmacology, neurosteroid, supplementation, therapy.

Graphical Abstract
[1]
Rainey, W.E.; Carr, B.R.; Sasano, H.; Suzuki, T.; Mason, J.I. Dissecting human adrenal androgen production. Trends Endocrinol. Metab., 2002, 13(6), 234-239.
[http://dx.doi.org/10.1016/S1043-2760(02)00609-4] [PMID: 12128283]
[2]
Baulieu, E.E.; Robel, P. Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulfate (DHEAS) as neuroactive neurosteroids. Proc. Natl. Acad. Sci. USA, 1998, 95(8), 4089-4091.
[http://dx.doi.org/10.1073/pnas.95.8.4089] [PMID: 9539693]
[3]
Friess, E.; Schiffelholz, T.; Steckler, T.; Steiger, A. Dehydroepiandrosterone -A neurosteroid. Eur. J. Clin. Invest., 2000, 30(Suppl. 3), 46-50.
[http://dx.doi.org/10.1046/j.1365-2362.2000.0300s3046.x] [PMID: 11281367]
[4]
Quinn, T.A.; Robinson, S.R.; Walker, D. Dehydroepiandrosterone (DHEA) and DHEA sulfate: Roles in brain function and disease. In: Sex Hormones in Neurodegenerative Processes and Diseases; Drevensek, Gorazd IntechOpen, 2018. Available from: https://www.intechopen.com/chapters/58381
[5]
Labrie, F.; Luu-The, V.; Bélanger, A.; Lin, S.X.; Simard, J.; Pelletier, G.; Labrie, C. Is dehydroepiandrosterone a hormone? J. Endocrinol., 2005, 187(2), 169-196.
[http://dx.doi.org/10.1677/joe.1.06264] [PMID: 16293766]
[6]
Klinge, C.M.; Clark, B.J.; Prough, R.A. Dehydroepiandrosterone research: Past, current, and future. Vitam. Horm., 2018, 108, 1-28.
[http://dx.doi.org/10.1016/bs.vh.2018.02.002] [PMID: 30029723]
[7]
Labrie, F. Luu, The, V.; Labrie, C.; Simard, J. DHEA and its transformation into androgens and estrogens in peripheral target tissues. Intracrinology. Front. Neuroendocrinol., 2001, 22(3), 185-212.
[http://dx.doi.org/10.1006/frne.2001.0216] [PMID: 11456468]
[8]
Berr, C.; Lafont, S.; Debuire, B.; Dartigues, J.F.; Baulieu, E.E. Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study. Proc. Natl. Acad. Sci. USA, 1996, 93(23), 13410-13415.
[http://dx.doi.org/10.1073/pnas.93.23.13410] [PMID: 8917605]
[9]
Sorwell, K.G.; Urbanski, H.F. Dehydroepiandrosterone and age-related cognitive decline. Age, 2010, 32(1), 61-67.
[http://dx.doi.org/10.1007/s11357-009-9113-4] [PMID: 19711196]
[10]
Roth, G.S.; Lane, M.A.; Ingram, D.K.; Mattison, J.A.; Elahi, D.; Tobin, J.D.; Muller, D.; Metter, E.J. Biomarkers of caloric restriction may predict longevity in humans. Science, 2002, 297(5582), 811.
[http://dx.doi.org/10.1126/science.1071851] [PMID: 12161648]
[11]
Li, R.EL.; Zha, N. Circulating dehydroepiandrosterone sulfate level and cardiovascular or all-cause mortality in the elderly population: A meta-analysis. Ann. Palliat. Med., 2020, 9(5), 3537-3545.
[http://dx.doi.org/10.21037/apm-20-441] [PMID: 32921089]
[12]
Mueller, J.W.; Gilligan, L.C.; Idkowiak, J.; Arlt, W.; Foster, P.A. The regulation of steroid action by sulfation and desulfation. Endocr. Rev., 2015, 36(5), 526-563.
[http://dx.doi.org/10.1210/er.2015-1036] [PMID: 26213785]
[13]
Tannenbaum, C.; Barrett-Connor, E.; Laughlin, G.A.; Platt, R.W. A longitudinal study of Dehydroepiandrosterone Sulphate (DHEAS) change in older men and women: The Rancho Bernardo Study. Eur. J. Endocrinol., 2004, 151(6), 717-725.
[http://dx.doi.org/10.1530/eje.0.1510717] [PMID: 15588238]
[14]
Loomba-Albrecht, L.A.; Styne, D.M. Hormonal control of puberty. In: Encyclopedia of Endocrine Diseases; 2nd ed.; Elsevier Inc., 2019; 5, p. 137-143. Available from: http://www.sciencedirect.com/topics/medicine-and-dentistry/adrenarche
[http://dx.doi.org/10.1016/B978-0-12-801238-3.65353-9]
[15]
Feldman, Witchel, S.; Plant, T.M. Puberty: Gonadarche and adrenarche. In: Yen & Jaffe's Reproductive Endocrinology; 7th ed.; Elsevier Inc., 2014; p. 377-421. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/adrenarche
[16]
Auchus, R.J.; Rainey, W.E. Adrenarche - Physiology, biochemistry and human disease. Clin. Endocrinol., 2004, 60(3), 288-296.
[http://dx.doi.org/10.1046/j.1365-2265.2003.01858.x] [PMID: 15008992]
[17]
Sahu, P.; Gidwani, B.; Dhongade, H.J. Pharmacological activities of dehydroepiandrosterone: A review. Steroids, 2020, 153, 108507.
[http://dx.doi.org/10.1016/j.steroids.2019.108507] [PMID: 31586606]
[18]
Samaras, N.; Samaras, D.; Frangos, E.; Forster, A.; Philippe, J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: Is treatment beneficial? Rejuvenation Res., 2013, 16(4), 285-294.
[http://dx.doi.org/10.1089/rej.2013.1425] [PMID: 23647054]
[19]
Webb, S.J.; Geoghegan, T.E.; Prough, R.A.; Michael Miller, K.K. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab. Rev., 2006, 38(1-2), 89-116.
[http://dx.doi.org/10.1080/03602530600569877] [PMID: 16684650]
[20]
Labrie, F.; Luu-The, V.; Labrie, C.; Bélanger, A.; Simard, J.; Lin, S.X.; Pelletier, G. Endocrine and intracrine sources of androgens in women: Inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr. Rev., 2003, 24(2), 152-182.
[http://dx.doi.org/10.1210/er.2001-0031] [PMID: 12700178]
[21]
Dhatariya, K.K.; Nair, K.S.; Sreekumaran, N. Dehydroepiandrosterone: Is there a role for replacement? Mayo Clin. Proc., 2003, 78(10), 1257-1273.
[http://dx.doi.org/10.4065/78.10.1257] [PMID: 14531485]
[22]
Huecker, M.R.; Bhutta, B.S.; Dominique, E. Adrenal insufficiency; Stat Pearls Publishing: Treasure Island, FL, 2022.
[23]
Davis, S.R.; Panjari, M.; Stanczyk, F.Z. Clinical review: DHEA replacement for postmenopausal women. J. Clin. Endocrinol. Metab., 2011, 96(6), 1642-1653.
[http://dx.doi.org/10.1210/jc.2010-2888] [PMID: 21411558]
[24]
Jefcoate, C. High-flux mitochondrial cholesterol trafficking, a specialized function of the adrenal cortex. J. Clin. Invest., 2002, 110(7), 881-890.
[http://dx.doi.org/10.1172/JCI0216771] [PMID: 12370263]
[25]
Maninger, N.; Wolkowitz, O.M.; Reus, V.I.; Epel, E.S.; Mellon, S.H. Neurobiological and neuropsychiatric effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS). Front. Neuroendocrinol., 2009, 30(1), 65-91.
[http://dx.doi.org/10.1016/j.yfrne.2008.11.002] [PMID: 19063914]
[26]
Hornsby, P. Aging of the human adrenal cortex. Ageing Res. Rev., 2002, 1(2), 229-242.
[http://dx.doi.org/10.1016/S1568-1637(01)00007-1] [PMID: 12039440]
[27]
Allolio, B.; Arlt, W. DHEA treatment: Myth or reality? Trends Endocrinol. Metab., 2002, 13(7), 288-294.
[http://dx.doi.org/10.1016/S1043-2760(02)00617-3] [PMID: 12163230]
[28]
Siiteri, P.K. The continuing saga of Dehydroepiandrosterone (DHEA). J. Clin. Endocrinol. Metab., 2005, 90(6), 3795-3796.
[http://dx.doi.org/10.1210/jc.2005-0852] [PMID: 15917487]
[29]
Longcope, C. The metabolism of dehydroepiandrosterone sulfate and dehydroepiandrosterone. Aging Male, 1998, 1(1), 51-55.
[http://dx.doi.org/10.3109/13685539809148602]
[30]
Labrie, F.; Luu-The, V.; Lin, S.X.; Simard, J.; Labrie, C. Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends Endocrinol. Metab., 2000, 11(10), 421-427.
[http://dx.doi.org/10.1016/S1043-2760(00)00342-8] [PMID: 11091120]
[31]
Frye, R.F.; Kroboth, P.D.; Kroboth, F.J.; Stone, R.A.; Folan, M.; Salek, F.S.; Pollock, B.G.; Linares, A.M.; Hakala, C. Sex differences in the pharmacokinetics of Dehydroepiandrosterone (DHEA) after single- and multiple-dose administration in healthy older adults. J. Clin. Pharmacol., 2000, 40(6), 596-605.
[http://dx.doi.org/10.1002/j.1552-4604.2000.tb05985.x] [PMID: 10868310]
[32]
Legrain, S.; Massien, C.; Lahlou, N.; Roger, M.; Debuire, B.; Diquet, B.; Chatellier, G.; Azizi, M.; Faucounau, V.; Porchet, H.; Forette, F.; Baulieu, E.E. Dehydroepiandrosterone replacement administration: Pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J. Clin. Endocrinol. Metab., 2000, 85(9), 3208-3217.
[PMID: 10999810]
[33]
Mo, Q.; Lu, S.; Simon, N.G. Dehydroepiandrosterone and its metabolites: Differential effects on androgen receptor trafficking and transcriptional activity. J. Steroid Biochem. Mol. Biol., 2006, 99(1), 50-58.
[http://dx.doi.org/10.1016/j.jsbmb.2005.11.011] [PMID: 16524719]
[34]
Acacio, B.D.; Stanczyk, F.Z.; Mullin, P.; Saadat, P.; Jafarian, N.; Sokol, R.Z. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men. Fertil. Steril., 2004, 81(3), 595-604.
[http://dx.doi.org/10.1016/j.fertnstert.2003.07.035] [PMID: 15037408]
[35]
Labrie, F.; Bélanger, A.; Labrie, C.; Candas, B.; Cusan, L.; Gomez, J.L. Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women. J. Steroid Biochem. Mol. Biol., 2007, 107(1-2), 57-69.
[http://dx.doi.org/10.1016/j.jsbmb.2007.02.007] [PMID: 17627814]
[36]
Labrie, F.; Cusan, L.; Gomez, J.L.; Martel, C.; Bérubé, R.; Bélanger, P.; Chaussade, V.; Deloche, C.; Leclaire, J. Changes in serum DHEA and eleven of its metabolites during 12-month percutaneous administration of DHEA. J. Steroid Biochem. Mol. Biol., 2008, 110(1-2), 1-9.
[http://dx.doi.org/10.1016/j.jsbmb.2008.02.003] [PMID: 18359622]
[37]
Traish, A.M.; Kang, H.P.; Saad, F.; Guay, A.T. Dehydroepiandrosterone (DHEA)-A precursor steroid or an active hormone in human physiology. J. Sex. Med., 2011, 8(11), 2960-2982.
[http://dx.doi.org/10.1111/j.1743-6109.2011.02523.x] [PMID: 22032408]
[38]
Cai, J.J.; Wen, J.; Jiang, W.H.; Lin, J.; Hong, Y.; Zhu, Y.S. Androgen actions on endothelium functions and cardiovascular diseases. J. Geriatr. Cardiol., 2016, 13(2), 183-196.
[PMID: 27168746]
[39]
Savineau, J.P.; Marthan, R.; Dumas de la Roque, E. Role of DHEA in cardiovascular diseases. Biochem. Pharmacol., 2013, 85(6), 718-726.
[http://dx.doi.org/10.1016/j.bcp.2012.12.004] [PMID: 23270992]
[40]
Wang, F.; He, Y.; O. Santos, H.; Sathian, B.; C Price, J.; Diao, J. The effects of Dehydroepiandrosterone (DHEA) supplementation on body composition and blood pressure: A meta-analysis of randomized clinical trials. Steroids, 2020, 163, 108710.
[http://dx.doi.org/10.1016/j.steroids.2020.108710] [PMID: 32745490]
[41]
Wu, T.T.; Chen, Y.; Zhou, Y.; Adi, D.; Zheng, Y.Y.; Liu, F.; Ma, Y.T.; Xie, X. Prognostic value of dehydroepiandrosterone sulfate for patients with cardiovascular disease: A systematic review and meta‐analysis. J. Am. Heart Assoc., 2017, 6(5), e004896.
[http://dx.doi.org/10.1161/JAHA.116.004896] [PMID: 28476876]
[42]
Brignardello, E.; Runzo, C.; Aragno, M.; Catalano, M.G.; Cassader, M.; Perin, P.C.; Boccuzzi, G. Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients. Diabetes Care, 2007, 30(11), 2922-2927.
[http://dx.doi.org/10.2337/dc07-1110] [PMID: 17704347]
[43]
Aoki, K.; Terauchi, Y. Effect of Dehydroepiandrosterone (DHEA) on diabetes mellitus and obesity. Vitam. Horm., 2018, 108, 355-365.
[http://dx.doi.org/10.1016/bs.vh.2018.01.008] [PMID: 30029734]
[44]
Wang, X.; Feng, H.; Fan, D.; Zou, G.; Han, Y.; Liu, L. The influence of Dehydroepiandrosterone (DHEA) on fasting plasma glucose, insulin levels and insulin resistance (HOMA-IR) index: A systematic review and dose response meta-analysis of randomized controlled trials. Complement. Ther. Med., 2020, 55, 102583.
[http://dx.doi.org/10.1016/j.ctim.2020.102583] [PMID: 33220623]
[45]
Nagaya, T.; Kondo, Y.; Okinaka, T. Serum dehydroepiandrosterone-sulfate reflects age better than health status, and may increase with cigarette smoking and alcohol drinking in middle-aged men. Aging Clin. Exp. Res., 2012, 24(2), 134-138.
[http://dx.doi.org/10.1007/BF03325159] [PMID: 22842832]
[46]
Stomati, M.; Monteleone, P.; Casarosa, E.; Quirici, B.; Puccetti, S.; Bernardi, F.; Genazzani, A.D.; Rovati, L.; Luisi, M.; Genazzani, A.R. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol. Endocrinol., 2000, 14(5), 342-363.
[http://dx.doi.org/10.3109/09513590009167703] [PMID: 11109974]
[47]
Lin, X.H.; Choi, I.S.; Koh, Y.A.; Cui, Y. Effects of combined bacille Calmette-Guérin and dehydroepiandrosterone treatment on established asthma in mice. Exp. Lung Res., 2009, 35(3), 250-261.
[http://dx.doi.org/10.1080/01902140802626656] [PMID: 19337907]
[48]
Morfin, R.; Lafaye, P.; Cotillon, A.C.; Nato, F.; Chmielewski, V.; Pompon, D. 7 alpha-hydroxy-dehydroepiandrosterone and immune response. Ann. N. Y. Acad. Sci., 2000, 917(1), 971-982.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05464.x] [PMID: 11268429]
[49]
Cao, J.; Yu, L.; Zhao, J.; Ma, H. Effect of dehydroepiandrosterone on the immune function of mice in vivo and in vitro. Mol. Immunol., 2019, 112, 283-290.
[http://dx.doi.org/10.1016/j.molimm.2019.06.004] [PMID: 31228660]
[50]
Piketty, C.; Jayle, D.; Leplege, A.; Castiel, P.; Ecosse, E.; Gonzalez-Canali, G.; Sabatier, B.; Boulle, N.; Debuire, B.; Le Bouc, Y.; Baulieu, E.E.; Kazatchkine, M.D. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin. Endocrinol., 2001, 55(3), 325-330.
[http://dx.doi.org/10.1046/j.1365-2265.2001.01310.x] [PMID: 11589675]
[51]
Fang, Y.H.; Hsieh, M.J.; Hung, M.S.; Lin, Y.C.; Kuo, L.T.; Lu, M.L.; Tzang, B.S.; Chen, V.C.H. Low Concentrations of dehydroepiandrosterone sulfate are associated with depression and fatigue in patients with non-small-cell lung cancer after chemotherapy. Neuropsychiatr. Dis. Treat., 2020, 16, 2103-2109.
[http://dx.doi.org/10.2147/NDT.S265182] [PMID: 32982248]
[52]
Williams, J.R. The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging. Lipids, 2000, 35(3), 325-331.
[http://dx.doi.org/10.1007/s11745-000-0529-7] [PMID: 10783010]
[53]
Knöferl, M.W.; Angele, M.K.; Catania, R.A.; Diodato, M.D.; Bland, K.I.; Chaudry, I.H. Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage. J. Appl. Physiol., 2003, 95(2), 529-535.
[http://dx.doi.org/10.1152/japplphysiol.01201.2002] [PMID: 12692147]
[54]
Meyer, P.; Meier, C.A. Focus on Dehydroepiandrosterone (DHEA). Rev. Med. Suisse, 2005, 1(6), 415-418.
[PMID: 15786645]
[55]
Vera-Lastra, O.; Vazquez, C.; Cruz-Dominguez, M.P.; Jara-Quezada, L.J.; Jara, L.J. Prolactin and dehydroepiandrosterone sulfate in women with active systemic lupus erythematosus of recent onset versus chronic inactive patients. Abstract in Arthritis Rheumatol., 2018, 70(10)
[56]
Hartkamp, A.; Geenen, R.; Godaert, G.L.R.; Bijl, M.; Bijlsma, J.W.J.; Derksen, R.H.W.M. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: A randomised controlled trial. Ann. Rheum. Dis., 2010, 69(6), 1144-1147.
[http://dx.doi.org/10.1136/ard.2009.117036] [PMID: 19854713]
[57]
Cao, J.; Zhang, H.; Yang, Z.; Zhao, J.; Ma, H. Effect of dehydroepiandrosterone on the immune response and gut microbiota in dextran sulfate sodium-induced colitis mice. Mol. Immunol., 2020, 118, 60-72.
[http://dx.doi.org/10.1016/j.molimm.2019.12.008] [PMID: 31855808]
[58]
De La Torre, B.; Hedman, M.; Befrits, R. Blood and tissue dehydroepiandrosterone sulphate levels and their relationship to chronic inflammatory bowel disease. Clin. Exp. Rheumatol., 1998, 16(5), 579-582.
[PMID: 9779307]
[59]
Rutkowski, K.; Sowa, P.; Rutkowska, T.J.; Kuryliszyn, M.A.; Rutkowski, R. Dehydroepiandrosterone (DHEA): Hypes and hopes. Drugs, 2014, 74(11), 1195-1207.
[http://dx.doi.org/10.1007/s40265-014-0259-8] [PMID: 25022952]
[60]
Priego, T.; Martín, A.I.; González-Hedstrom, D.; Granado, M.; López-Calderon, A. Role of hormones in sarcopenia. Vitam. Horm., 2021, 115, 535-570.
[http://dx.doi.org/10.1016/bs.vh.2020.12.021] [PMID: 33706961]
[61]
Tsuji, K.; Furutama, D.; Tagami, M.; Ohsawa, N. Specific binding and effects of Dehydroepiandrosterone Sulfate (DHEA-S) on skeletal muscle cells: Possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy. Life Sci., 1999, 65(1), 17-26.
[http://dx.doi.org/10.1016/S0024-3205(99)00215-5] [PMID: 10403489]
[62]
Hu, Y.; Wan, P.; An, X.; Jiang, G. Impact of Dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and BMI in elderly women: A meta-analysis of randomized controlled trials. Complement. Ther. Med., 2021, 56, 102620.
[http://dx.doi.org/10.1016/j.ctim.2020.102620] [PMID: 33220453]
[63]
Sato, K.; Iemitsu, M. The role of Dehydroepiandrosterone (DHEA) in skeletal muscle. Vitam. Horm., 2018, 108, 205-221.
[http://dx.doi.org/10.1016/bs.vh.2018.03.002] [PMID: 30029727]
[64]
Villareal, D.T.; Holloszy, J.O. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am. J. Physiol. Endocrinol. Metab., 2006, 291(5), E1003-E1008.
[http://dx.doi.org/10.1152/ajpendo.00100.2006] [PMID: 16787962]
[65]
Kirby, D.J.; Buchalter, D.B.; Anil, U.; Leucht, P. DHEA in bone: The role in osteoporosis and fracture healing. Arch. Osteoporos., 2020, 15(1), 84.
[http://dx.doi.org/10.1007/s11657-020-00755-y] [PMID: 32504237]
[66]
Huang, K.; Wu, L. Dehydroepiandrosterone: Molecular mechanisms and therapeutic implications in osteoarthritis. J. Steroid Biochem. Mol. Biol., 2018, 183, 27-38.
[http://dx.doi.org/10.1016/j.jsbmb.2018.05.004] [PMID: 29787833]
[67]
Lin, L.T.; Tsui, K.H. The relationships between serum DHEA-S and AMH levels in infertile women: A retrospective cross-sectional study. J. Clin. Med., 2021, 10(6), 1211.
[http://dx.doi.org/10.3390/jcm10061211] [PMID: 33803980]
[68]
Elprince, M.; Kishk, E.A.; Metawie, O.M.; Albiely, M.M. Ovarian stimulation after dehydroepiandrosterone supplementation in poor ovarian reserve: A randomized clinical trial. Arch. Gynecol. Obstet., 2020, 302(2), 529-534.
[http://dx.doi.org/10.1007/s00404-020-05603-5] [PMID: 32451660]
[69]
Li, Y.; Ren, J.; Li, N.; Liu, J.; Tan, S.C.; Low, T.Y.; Ma, Z. A dose-response and meta-analysis of Dehydroepiandrosterone (DHEA) supplementation on testosterone levels: Perinatal prediction of randomized clinical trials. Exp. Gerontol., 2020, 141, 111110.
[http://dx.doi.org/10.1016/j.exger.2020.111110] [PMID: 33045358]
[70]
Davis, S.R.; Wahlin-Jacobsen, S. Testosterone in women-The clinical significance. Lancet Diabetes Endocrinol., 2015, 3(12), 980-992.
[http://dx.doi.org/10.1016/S2213-8587(15)00284-3] [PMID: 26358173]
[71]
Pérez-Neri, I.; Montes, S. Ojeda, Lopez-C.; Ramírez, Bermudes- J.; Ríos, C. Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(5), 1118-1130.
[http://dx.doi.org/10.1016/j.pnpbp.2007.12.001] [PMID: 18280022]
[72]
Strac, D.S.; Konjevod, M.; Perkovic, M.N.; Tudor, L.; Erjavec, G.N.; Pivac, N. Dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) in Alzheimer’s disease. Curr. Alzheimer Res., 2020, 17(2), 141-157.
[http://dx.doi.org/10.2174/1567205017666200317092310] [PMID: 32183671]
[73]
Ritsner, M.S. The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia. Neuroscience, 2011, 191, 91-100.
[http://dx.doi.org/10.1016/j.neuroscience.2011.04.017] [PMID: 21549182]
[74]
Boiko, A.S.; Mednova, I.A.; Kornetova, E.G.; Bokhan, N.A.; Semke, A.V.; Loonen, A.J.M.; Ivanova, S.A. Cortisol and DHEAS related to metabolic syndrome in patients with schizophrenia. Neuropsychiatr. Dis. Treat., 2020, 16, 1051-1058.
[http://dx.doi.org/10.2147/NDT.S247161] [PMID: 32368067]
[75]
Mòdol, L.; Darbra, S.; Pallarès, M. Neurosteroids infusion into the CA1 hippocampal region on exploration, anxiety-like behaviour and aversive learning. Behav. Brain Res., 2011, 222(1), 223-229.
[http://dx.doi.org/10.1016/j.bbr.2011.03.058] [PMID: 21463656]
[76]
Samardzic, J.; Hencic, B.; Jancic, J.; Jadzic, D.; Djuric, M.; Obradovic, D.I.; Svob-Strac, D. Neurosteroid dehydroepiandrosterone improves active avoidance retrieval and induces antidepressant-like behavior in rats. Neurosci. Lett., 2017, 660, 17-21.
[http://dx.doi.org/10.1016/j.neulet.2017.09.013] [PMID: 28893591]
[77]
Fedotova, J.; Sapronov, N. Behavioral effects of dehydroepiandrosterone in adult male rats. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2004, 28(6), 1023-1027.
[http://dx.doi.org/10.1016/j.pnpbp.2004.05.037] [PMID: 15380863]
[78]
Campbell, B. DHEAS and human development: An evolutionary perspective. Front. Endocrinol., 2020, 11, 101.
[http://dx.doi.org/10.3389/fendo.2020.00101] [PMID: 32194506]
[79]
Pan, X.; Wu, X.; Kaminga, A.C.; Wen, S.W.; Liu, A. Dehydroepiandrosterone and dehydroepiandrosterone sulfate in Alzheimer’s disease: A systematic review and meta-analysis. Front. Aging Neurosci., 2019, 11, 61.
[http://dx.doi.org/10.3389/fnagi.2019.00061] [PMID: 30983988]
[80]
Strac, D.S.; Samardzic, J.; Erhardt, J.; Krsnik, Z.; Martinovic, J.; Drakulic, D.; Tudor, L.; Nikolac-Perkovic, M. Nedic, Erjavec, G.; Pivac, N. In vitro and in vivo studies of prolonged DHEA(S) treatment. In: Advances in Medicine and Biology; Berhardt, L., Ed.; NOVA Science Publishers: New York, 2017.
[81]
Samardzic, J.; Borovcanin, M.; Djukic-Dejanovic, S.; Jancic, J.; Djuric, M.; Obradovic, D. In vivo methodology in behavioural pharmacology - where are we now? Vojnosanit. Pregl., 2017, 74(4), 354-360.
[http://dx.doi.org/10.2298/VSP150616106S]
[82]
Samardzic, J.; Jadzic, D.; Hencic, B.; Jancic, J.; Strac, D.S. GABA/Glutamate Balance: A key for normal brain functioning. In: GABA and Glutamate; Samardzic, J., Ed.; IntechOpen: London, 2018.
[83]
Svob Strac, D.; Vlainic, J.; Samardzic, J.; Erhardt, J.; Krsnik, Z. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice. Drug Des. Devel. Ther., 2016, 10, 1201-1215.
[http://dx.doi.org/10.2147/DDDT.S102102] [PMID: 27051273]
[84]
Švob-Štrac, D. Jazvinšćak, Jemberk, M.; Erhardt, J.; Mirković Kos, K.; Peričić D. Modulation of recombinant GABA(A) receptors by neurosteroid dehydroepiandrosterone sulfate. Pharmacology, 2012, 89(3-4), 163-171.
[http://dx.doi.org/10.1159/000336058] [PMID: 22433179]
[85]
Maurice, T.; Phan, V.L.; Urani, A.; Guillemain, I. Differential involvement of the sigma 1 (σ 1) receptor in the anti-amnesic effect of neuroactive steroids, as demonstrated using an in vivo antisense strategy in the mouse. Br. J. Pharmacol., 2001, 134(8), 1731-1741.
[http://dx.doi.org/10.1038/sj.bjp.0704355] [PMID: 11739250]
[86]
Pérez-Neri, I.; Méndez-Sanchez, I.; Montes, S.; Ríos, C. Acute dehydroepiandrosterone treatment exerts different effects on dopamine and serotonin turnover ratios in the rat corpus striatum and nucleus accumbens. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(6), 1584-1589.
[http://dx.doi.org/10.1016/j.pnpbp.2008.06.002] [PMID: 18585426]
[87]
Monnet, F.P.; Mahé, V.; Robel, P.; Baulieu, E.E. Neurosteroids, via sigma receptors, modulate the [3H]norepinephrine release evoked by N-methyl-D-aspartate in the rat hippocampus. Proc. Natl. Acad. Sci. USA, 1995, 92(9), 3774-3778.
[http://dx.doi.org/10.1073/pnas.92.9.3774] [PMID: 7731982]
[88]
Laurine, E.; Lafitte, D.; Grégoire, C.; Sérée, E.; Loret, E.; Douillard, S.; Michel, B.; Briand, C.; Verdier, J.M. Specific binding of dehydroepiandrosterone to the N terminus of the microtubule-associated protein MAP2. J. Biol. Chem., 2003, 278(32), 29979-29986.
[http://dx.doi.org/10.1074/jbc.M303242200] [PMID: 12775713]
[89]
Charalampopoulos, I.; Margioris, A.N.; Gravanis, A. Neurosteroid dehydroepiandrosterone exerts anti-apoptotic effects by membrane-mediated, integrated genomic and non-genomic pro-survival signaling pathways. J. Neurochem., 2008, 107(5), 1457-1469.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05732.x] [PMID: 19013851]
[90]
Lazaridis, I.; Charalampopoulos, I.; Alexaki, V.I.; Avlonitis, N.; Pediaditakis, I.; Efstathopoulos, P.; Calogeropoulou, T.; Castanas, E.; Gravanis, A. Neurosteroid dehydroepiandrosterone interacts with Nerve Growth Factor (NGF) receptors, preventing neuronal apoptosis. PLoS Biol., 2011, 9(4), e1001051.
[http://dx.doi.org/10.1371/journal.pbio.1001051] [PMID: 21541365]
[91]
George, O.; Vallée, M.; Le Moal, M.; Mayo, W. Neurosteroids and cholinergic systems: Implications for sleep and cognitive processes and potential role of age-related changes. Psychopharmacology, 2006, 186(3), 402-413.
[http://dx.doi.org/10.1007/s00213-005-0254-6] [PMID: 16416333]
[92]
Schverer, M.; Lanfumey, L.; Baulieu, E.E.; Froger, N.; Villey, I. Neurosteroids: Non-genomic pathways in neuroplasticity and involvement in neurological diseases. Pharmacol. Ther., 2018, 191, 190-206.
[http://dx.doi.org/10.1016/j.pharmthera.2018.06.011] [PMID: 29953900]
[93]
Mellon, S.H. Neurosteroid regulation of central nervous system development. Pharmacol. Ther., 2007, 116(1), 107-124.
[http://dx.doi.org/10.1016/j.pharmthera.2007.04.011] [PMID: 17651807]
[94]
Compagnone, N.A.; Mellon, S.H. Dehydroepiandrosterone: A potential signalling molecule for neocortical organization during development. Proc. Natl. Acad. Sci. USA, 1998, 95(8), 4678-4683.
[http://dx.doi.org/10.1073/pnas.95.8.4678] [PMID: 9539798]
[95]
Gallo, M.; Aragno, M.; Gatto, V.; Tamagno, E.; Brignardello, E.; Manti, R.; Danni, O.; Boccuzzi, G. Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line. Eur. J. Endocrinol., 1999, 141(1), 35-39.
[http://dx.doi.org/10.1530/eje.0.1410035] [PMID: 10407220]
[96]
Tamagno, E.; Aragno, M.; Boccuzzi, G.; Gallo, M.; Parola, S.; Fubini, B.; Poli, G.; Danni, O. Oxygen free radical scavenger properties of dehydroepiandrosterone. Cell Biochem. Funct., 1998, 16(1), 57-63.
[http://dx.doi.org/10.1002/(SICI)1099-0844(199803)16:1<57:AID-CBF771>3.0.CO;2-S] [PMID: 9519460]
[97]
Rojo, A.I.; McBean, G.; Cindric, M.; Egea, J.; López, M.G.; Rada, P.; Zarkovic, N.; Cuadrado, A. Redox control of microglial function: Molecular mechanisms and functional significance. Antioxid. Redox Signal., 2014, 21(12), 1766-1801.
[http://dx.doi.org/10.1089/ars.2013.5745] [PMID: 24597893]
[98]
Kurata, K.; Takebayashi, M.; Morinobu, S.; Yamawaki, S. beta-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-methyl-D-aspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms. J. Pharmacol. Exp. Ther., 2004, 311(1), 237-245.
[http://dx.doi.org/10.1124/jpet.104.067629] [PMID: 15175425]
[99]
Cheng, Z.X.; Lan, D.M.; Wu, P.Y.; Zhu, Y.H.; Dong, Y.; Ma, L.; Zheng, P. Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors. Exp. Neurol., 2008, 210(1), 128-136.
[http://dx.doi.org/10.1016/j.expneurol.2007.10.004] [PMID: 18035354]
[100]
Görlach, A.; Bertram, K.; Hudecova, S.; Krizanova, O. Calcium and ROS: A mutual interplay. Redox Biol., 2015, 6, 260-271.
[http://dx.doi.org/10.1016/j.redox.2015.08.010] [PMID: 26296072]
[101]
Kipper-Galperin, M.; Galilly, R.; Danenberg, H.D.; Brenner, T. Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor alpha and interleukin-6 [correction of interlukin-6] in astrocytes. Int. J. Dev. Neurosci., 1999, 17(8), 765-775.
[http://dx.doi.org/10.1016/S0736-5748(99)00067-2] [PMID: 10593612]
[102]
Vieira-Marques, C.; Arbo, B.D.; Ruiz-Palmero, I.; Ortiz-Rodriguez, A.; Ghorbanpoor, S.; Kucharski, L.C.; Arevalo, M.A.; Garcia-Segura, L.M.; Ribeiro, M.F.M. Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation. Brain Res., 2016, 1644, 176-182.
[http://dx.doi.org/10.1016/j.brainres.2016.05.014] [PMID: 27174000]
[103]
Brown, R.; Han, Z.; Cascio, C.; Papadopoulos, V. Oxidative stress-mediated DHEA formation in Alzheimer’s disease pathology. Neurobiol. Aging, 2003, 24(1), 57-65.
[http://dx.doi.org/10.1016/S0197-4580(02)00048-9] [PMID: 12493551]
[104]
Weill-Engerer, S.; David, J.P.; Sazdovitch, V.; Liere, P.; Eychenne, B.; Pianos, A.; Schumacher, M.; Delacourte, A.; Baulieu, E.E.; Akwa, Y. Neurosteroid quantification in human brain regions: Comparison between Alzheimer’s and nondemented patients. J. Clin. Endocrinol. Metab., 2002, 87(11), 5138-5143.
[http://dx.doi.org/10.1210/jc.2002-020878] [PMID: 12414884]
[105]
Gandy, S. Molecular basis for anti-amyloid therapy in the prevention and treatment of Alzheimer’s disease. Neurobiol. Aging, 2002, 23(6), 1009-1016.
[http://dx.doi.org/10.1016/S0197-4580(02)00125-2] [PMID: 12470796]
[106]
Li, L.; Xu, B.; Zhu, Y.; Chen, L.; Sokabe, M.; Chen, L. DHEA prevents Aβ25–35-impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling. Neuropharmacology, 2010, 59(4-5), 323-333.
[http://dx.doi.org/10.1016/j.neuropharm.2010.02.009] [PMID: 20167228]
[107]
Grimm, A.; Biliouris, E.E.; Lang, U.E.; Götz, J.; Mensah-Nyagin, A.G.; Eckert, A. Sex hormone-related neurosteroids differentially rescue bioenergetic deficits induced by amyloid-β or hyperphosphorylated tau protein. Cell. Mol. Life Sci., 2016, 73(1), 201-215.
[http://dx.doi.org/10.1007/s00018-015-1988-x] [PMID: 26198711]
[108]
Buée, L.; Bussière, T.; Buée-Scherrer, V.; Delacourte, A.; Hof, P.R. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Brain Res. Rev., 2000, 33(1), 95-130.
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[109]
Schaeffer, V.; Patte-Mensah, C.; Eckert, A.; Mensah-Nyagan, A.G. Modulation of neurosteroid production in human neuroblastoma cells by Alzheimer’s disease key proteins. J. Neurobiol., 2006, 66(8), 868-881.
[http://dx.doi.org/10.1002/neu.20267] [PMID: 16673391]
[110]
Francis, P.T.; Palmer, A.M.; Snape, M.; Wilcock, G.K. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 66(2), 137-147.
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[111]
Kása, P.; Rakonczay, Z.; Gulya, K. The cholinergic system in Alzheimer’s disease. Prog. Neurobiol., 1997, 52(6), 511-535.
[http://dx.doi.org/10.1016/S0301-0082(97)00028-2] [PMID: 9316159]
[112]
Lawrence, A.D.; Sahakian, B.J. Alzheimer disease, attention, and the cholinergic system. Alzheimer Dis. Assoc. Disord., 1995, 9(Suppl. 2), 37-49.
[http://dx.doi.org/10.1097/00002093-199501002-00008] [PMID: 8534423]
[113]
Van Niekerk, J.K.; Huppert, F.A.; Herbert, J. Salivary cortisol and DHEA: Association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinology, 2001, 26(6), 591-612.
[http://dx.doi.org/10.1016/S0306-4530(01)00014-2] [PMID: 11403980]
[114]
Kritz-Selverstein, D.; Von Mühlen, D.; Laughlin, G.A.; Bettencourt, R. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: The DHEA and Well-Ness (DAWN). Trial. J. Am. Geriatr. Soc., 2008, 56(7), 1292-1298.
[http://dx.doi.org/10.1111/j.1532-5415.2008.01768.x] [PMID: 18482290]
[115]
Wang, X.; Feero, W.G. Does dehydroepiandrosterone decrease the risk or progression of Alzheimer’s dementia? Evidence-Based Practice, 2019, 22(2), 26.
[http://dx.doi.org/10.1097/EBP.0000000000000162]
[116]
Dayal, M.; Sammel, M.D.; Zhao, J.; Hummel, A.C.; Vandenbourne, K.; Barnhart, K.T. Supplementation with DHEA: Effect on muscle size, strength, quality of life, and lipids. J. Womens Health, 2005, 14(5), 391-400.
[http://dx.doi.org/10.1089/jwh.2005.14.391] [PMID: 15989411]
[117]
Wolf, O.T.; Kudielka, B.M.; Hellhammer, D.H.; Hellhammer, J.; Kirschbaum, C. Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor. Psychoneuroendocrinology, 1998, 23(6), 617-629.
[http://dx.doi.org/10.1016/S0306-4530(98)00032-8] [PMID: 9802132]
[118]
Suzuki, T.; Suzuki, N.; Daynes, R.A.; Engleman, E.G. Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin. Immunol. Immunopathol., 1991, 61(2), 202-211.
[http://dx.doi.org/10.1016/S0090-1229(05)80024-8] [PMID: 1833106]
[119]
Wolkowitz, O.M.; Kramer, J.H.; Reus, V.I.; Costa, M.M.; Yaffe, K.; Walton, P.; Raskind, M.; Peskind, E.; Newhouse, P.; Sack, D.; De Souza, E.; Sadowsky, C.; Roberts, E. DHEA treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled study. Neurology, 2003, 60(7), 1071-1076.
[http://dx.doi.org/10.1212/01.WNL.0000052994.54660.58] [PMID: 12682308]
[120]
Yamada, S.; Akishita, M.; Fukai, S.; Ogawa, S.; Yamaguchi, K.; Matsuyama, J.; Kozaki, K.; Toba, K.; Ouchi, Y. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr. Gerontol. Int., 2010, 10(4), 280-287.
[http://dx.doi.org/10.1111/j.1447-0594.2010.00625.x] [PMID: 20497239]

© 2024 Bentham Science Publishers | Privacy Policy