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Sensitivity to androgens: beyond the well-known facts

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Gonadal and extragonadal effects of testosterone in males have been extensively investigated in recent years. To date, there is no doubt that testosterone deficiency in males is associated with increased risk of obesity, type 2 diabetes mellitus, hypertension, and atherosclerosis. Sensitivity to androgens determined by the length of CAG-repeats in the androgen receptor gene is one of the underlying mechanisms of testosterone action. Increase in the number of CAG-repeats reduces activity of androgen receptors, which manifests in the form of low sensitivity to testosterone. On the contrary, decrease in the number of trinucleotide repeats is accompanied by increased sensitivity of the receptors to androgens. This review discusses the effect of androgen receptor gene polymorphism on embryogenesis and sex differentiation, regulation of spermatogenesis, progression of cancer and benign prostatic hyperplasia, symptoms of hypogonadism, control of carbohydrate and lipid metabolism, bone mineral density, vascular endothelium, response to replacement therapy with testosterone, as well as on the psychosocial aspects of personality in males. Implementation of the study of androgen receptor gene polymorphism into clinical practice will enable not only predicting male fertility or the risk of developing prostate cancer, but also selecting an individual therapy for testosterone deficiency.

Irina A. Khripun

Rostov State Medical University

Author for correspondence.
Email: khripun.irina@gmail.com
ORCID iD: 0000-0003-0284-295X
SPIN-code: 8630-4828

Russian Federation, 29, Nachitsevanskij, Rostov-on-Don, 344022


Sergey V. Vorobyev

Rostov State Medical University

Email: endocrinrosov@mail.ru
ORCID iD: 0000-0001-7884-2433
SPIN-code: 9773-6100

Russian Federation, 29, Nachitsevanskij, Rostov-on-Don, 344022

MD, PhD, Professor

  1. Omim.Org [Internet]. Androgen Receptor; Ar [Cited 2018 Sep 26]. Available From: https://www.omim.org/entry/313700
  2. Zitzmann M. Hypogonadism: biochemical diagnosis, treatment, and the myth of uniform thresholds. J Mens Health 2013;10(3):73-75. doi: https://doi.org/10.1089/jomh.2009.00030
  3. Limer KL, Pye SR, Thomson W, et al. Genetic variation in sex hormone genes influences heel ultrasound parameterso in middle-aged and elderly men: results from the European male aging study (EMAS). J Bone Miner Res. 2009;24(2):314-323. doi: https://doi.org/10.1359/jbmr.080912
  4. Zitzmann M. Mechanisms of disease: pharmacogenetics of testosterone therapy in hypogonadal men. Nat Clin Pract Urol. 2007;4(3):161-166. doi: https://doi.org/10.1038/ncpuro0706
  5. Guadalupe-Grau A, Rodriguez-Gonzalez FG, Ponce-Gonza lez JG, et al. Bone mass and the CAG and GGN androgen receptor polymorphisms in young men. Plos One. 2010;5(7):E11529. doi: https://doi.org/10.1371/journal.pone.0011529
  6. Rodriguez-Garcia L, Ponce-Gonzalez JG, Gonzalez-Henriquez JJ, et al. Androgen receptor CAG and GGN repeat polymorphisms and bone mass in boys and girls. Nutr Hosp. 2015;32(6):2633-2639. doi: https://doi.org/10.3305/nh.2015.32.6.9767
  7. Stiger F, Brandstrom H, Gillberg P, et al. Association between repeat length of Exon 1 CAG microsatellite in the androgen receptor and bone density in men is modulated by sex hormone levels. Calcif Tissue Int. 2008;82(6):427-435. doi: https://doi.org/10.1007/s00223-008-9128-3
  8. Canale D, Caglieresi C, Moschini C, et al. Androgen receptor polymorphism (CAG repeats) and androgenicity. Clin Endocrinol (Oxf.). 2005;63(3):356-361. doi: https://doi.org/10.1111/j.1365-2265.2005.02354.x
  9. Grassetti D, Giannandrea F, Paoli D, et al. Androgen receptor polymorphisms and testicular cancer risk. Andrology. 2015;3(1):27-33. doi: https://doi.org/10.1111/j.2047-2927.2014.00252.x
  10. Stanworth RD, Akhtar S, Channer KS, Jones TH. The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: times 2 Sub-Study. Eur J Endocrinol. 2014;170(2):193-200. doi: https://doi.org/10.1530/eje-13-0703
  11. Giovannucci E, Stampfer MJ, Chan A, et al. CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. Physicians. Prostate. 1999;39(2): 130-134. doi: https://doi.org/10.1002/(sici)1097-0045(19990501)39:2<130:: aid-pros8>3.0.co;2-#
  12. Giovannucci E, Platz EA, Stampfer MJ, et al. The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia. Urology. 1999;53(1):121-125. doi: https://doi.org/10.1016/s0090-4295(98)00468-3
  13. Коган М.И., Киреев А.Ю. Различия уровней тестостерона и полиморфизма андрогенового рецептора у пациентов с симптомной доброкачественной гиперплазией простаты в зависимости от сексуальной активности. // Андрология и генитальная хирургия. — 2009. — Т. 10. — №2. — C. 118. [Kogan MI, Kireev AYu. Razlichiya urovney testosterona i polimorfizma androgenovogo retseptora u patsientov s simptomnoy dobrokachestvennoy giperplaziey prostaty v zavisimosti ot seksual’noy aktivnosti. Andrology and Genital Surgery Journal. 2009;10(2):118. (In Russ.)].
  14. Giagulli VA, Carbone MD, De Pergola G, et al. Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility? J Assist Reprod Genet. 2014. doi: https://doi.org/10.1007/s10815-014-0221-4
  15. Delli Muti N, Tirabassi G, Buldreghini E, et al. Synergistic effect of androgen receptor (CAG repeat length) and endothelial nitric oxide synthase (Glu298asp Variant) gene polymorphisms on seminal parameters in men with idiopathic oligoasthenozoospermia. Endocrine. 2014;47(1):322-324. doi: https://doi.org/10.1007/s12020-014-0193-2
  16. Xiao F, Lan A, Lin Z, et al. Impact of CAG repeat length in the androgen receptor gene on male infertility — a metaanalysis. Reprod Biomed Online. 2016;33(1):39-49. doi: https://doi.org/10.1016/j.rbmo.2016.03.012
  17. Finsterer J, Soraru G. Onset manifestations of spinal and bulbar muscular atrophy (Kennedy’s disease). J Mol Neurosci. 2016; 58(3):321-329. doi: https://doi.org/10.1007/s12031-015-0663-x
  18. Schneider G, Nienhaus K, Gromoll J, et al. Aging males’ symptoms in relation to the genetically determined androgen receptor CAG polymorphism, sex hormone levels and sample membership. Psychoneuroendocrinology. 2010;35(4):578-587. doi: https://doi.org/10.1016/j.psyneuen.2009.09.008
  19. Liu CC, Lee YC, Wang CJ, et al. The impact of androgen receptor CAG repeat polymorphism on andropausal symptoms in different serum testosterone levels. J Sex Med. 2012;9(9):2429-2437. doi: https://doi.org/10.1111/j.1743-6109.2012.02672.x
  20. Schneider G, Nienhaus K, Gromoll J, et al. Sex gormone levels, genetic androgen receptor polymorphism, and anxiety in >/=50-year-old males. J Sex Med. 2011;8(12):3452-3464. doi: https://doi.org/10.1111/j.1743-6109.2011.02443.x
  21. Schneider G, Nienhaus K, Gromoll J, et al. Depressive symptoms in men aged 50 years and older and their relationship to genetic androgen receptor polymorphism and sex hormone levels in three different samples. Am J Geriatr Psychiatry. 2011;19(3):274-283. doi://https://doi.org/10.1097/jgp.0b013e381e70c22
  22. Celec P, Tretinarova D, Minarik G, et al. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys. Plos One. 2013;8(1):E54751. doi: https://doi.org/10.1371/journal.pone.0054751
  23. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. X-Chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab. 2004;89(12):6208-6217. doi: https://doi.org/10.1210/jc.2004-1424
  24. Hare L, Bernard P, Sanchez FJ, et al. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biol Psychiatry. 2009;65(1):93-96. doi: https://doi.org/10.1016/j.biopsych.2008.08.033
  25. Zitzmann M, Gromoll J, Von Eckardstein A, Nieschlag E. The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia. 2003;46(1):31-39. doi: https://doi.org/10.1007/s00125-002-0980-9
  26. Stanworth RD, Kapoor D, Channer KS, Jones TH. Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes. Clin Endocrinol (Oxf). 2011;74(5):624-630. doi: https://doi.org/10.1111/j.1365-2265.2011.03969.x
  27. Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab. 2007;92(10):3844-3853. doi: https://doi.org/10.1210/jc.2007-0620
  28. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharmacogenetic study. J Clin Endocrinol Metab. 2003;88(5):2049-2054. doi: https://doi.org/10.1210/jc.2002-021947
  29. Zitzmann M, Brune M, Kornmann B, et al. The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity. J Clin Endocrinol Metab. 2001;86(10):4867-4873. doi: https://doi.org/10.1210/jcem.86.10.7889
  30. Хрипун И.А., Воробьев С.В., Моргунов М.Н., Коган М.И. Функция эндотелия у мужчин с сахарным диабетом 2-го типа, не имеющих клинических признаков сердечно-сосудистых заболеваний. // Сахарный диабет. — 2016. — Т. 19. — №5. — С. 383-387. [Khripun IA, Vorobyev SV, Morgunov MN, Kogan MI. Endothelial function in men with type 2 diabetes without clinical signs of cardiovascular disease. Diabetes Mellitus. 2016;19(5):383-387. (In Russ.)]. doi: https://doi.org/10.14341/dm8017
  31. Van Sloten TT, Henry RM, Dekker JM, et al. Endothelial dysfunction plays a key role in increasing cardiovascular risk in type 2 diabetes: the Hoorn Study. Hypertension. 2014;64(6):1299-1305. doi: https://doi.org/10.1161/hypertensionaha.114.04221
  32. Хрипун И.А., Воробьев С.В., Пузырева В.П., и др. Дисфункция эндотелия как следствие андрогенного дефицита у мужчин с сахарным диабетом 2-го типа. // Современные проблемы науки и образования. — 2015. — № 6. [Khripun IA, Vorobyev SV, Puzyreva VP, et al. Dysfunction of endothelium, as a result of androgen deficiency in men with type 2 diabetes. Modern Problems Of Science And Education. 2015;(6). (In Russ.)].
  33. Kelly DM, Jones TH. Testosterone and cardiovascular risk in men. Front Horm Res. 2014;43:1-20. doi: https://doi.org/10.1159/000360553
  34. Хрипун И.А., Воробьев С.В., Коган М.И. Взаимосвязь полиморфизма гена рецептора андрогенов и функции эндотелия у мужчин с сахарным диабетом 2-го типа. // Сахарный диабет. — 2015. — Т. 18. — №4. — С. 35-40. [Khripun IA, Vorobyev SV, Kogan MI. Association of the polymorphism in the androgen receptor gene and endothelial function in men with type 2 diabetes. Diabetes Mellitus. 2015;18(4):35-40. (In Russ.)]. doi: https://doi.org/10.14341/dm7622

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