Androgen, androgen receptor and polycystic ovary syndrome

doi:10.16098/j.issn.0529-1356.2018.01.023

Abstract

Abstract:

Polycystic ovary syndrome (PCOS), with a prevalence of 5%-10%, is the most common endocrine and metabolic dysfunction of reproductive age women. However, the underlying mechanism has not been fully elucidated. Hyperandrogenism is the leading defect in PCOS patients, especially local androgen secretion by the ovary is the key element for PCOS pathogenesis. Androgen activates androgen receptor (AR), so the role of AR is an indispensable factor. This review focuses on the functions of androgen and AR in PCOS pathogenesis.

Key words: Androgen, Androgen receptor, Hyperandrogenism, Polycystic ovary syndrome

YANG Mei LIN Hai-wei ZHANG Hong-quan XU Xiao-ming CHEN Xi. Androgen, androgen receptor and polycystic ovary syndrome[J]. Acta Anatomica Sinica, 2018, 49(1): 132-136.

References

［1］Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview［J］. Endocr Rev, 2002, 23(2): 175-200.

［2］Shah NA, Antoine HJ, Pall M, et al. Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome［J］. J Clin Endocrinol Metab, 2008, 93(5): 1939-1945.

［3］Bennett NC, Gardiner RA, Hooper JD, et al. Molecular cell biology of androgen receptor signalling［J］. Int J Biochem Cell Biol, 2010, 42(6): 813-827.

［4］Walters KA, Middleton LJ, Joseph SR, et al. Targeted loss of androgen receptor signaling in murine granulosa cells of preantral and antral follicles causes female subfertility［J］. Biol Reprod, 2012,87(6): 151.

［5］Yang M, Du J, Lu D, et al. Increased expression of kindlin 2 in luteinized granulosa cells correlates with androgen receptor level in patients with polycystic ovary syndrome having hyperandrogenemia［J］. Reprod Sci, 2014, 21(6): 696-703.

［6］Sen A, Hammes SR. Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function［J］. Mol Endocrinol, 2010, 24(7): 1393-1403.

［7］Cheng XB, Jimenez M, Desai R, et al. Characterizing the neuroendocrine and ovarian defects of androgen receptor-knockout female mice［J］. Am J Physiol Endocrinol Metab, 2013, 305(6): E717-726.

［8］Wang RS, Chang HY, Kao SH, et al. Abnormal mitochondrial function and impaired granulose cell differentiation in androgen receptor knockout mice［J］. Int J Mol Sci, 2015, 16(5): 9831-9849.

［9］Gervásio CG, Bernuci MP, Silva-de-Sá MF, et al. The role of androgen hormones in early follicular development［J］. ISRN Obstet Gynecol, 2014, 2014: 818010.

［10］Zangmo R, Singh N, Kumar S, et al. Role of dehydroepiandrosterone in improving oocyte and embryo quality in IVF cycles［J］. Reprod Biomed Online, 2014, 28(6): 743-747.

［11］Narkwichean A, Maalouf W, Campbell BK, et al. Efficacy of dehydroepiandrosterone to improve ovarian response in women with diminished ovarian reserve: a meta-analysis［J］. Reprod Biol Endocrinol, 2013, 11: 44.

［12］Pierre A, Peigné M, Grynberg M, et al. Loss of LH-induced down-regulation of anti-Müllerian hormone receptor expression may contribute to anovulation in women with polycystic ovary syndrome［J］. Hum Reprod. 2013, 28(3): 762-769.

［13］Bhide P, Dilgil M, Gudi A, et al. Each small antral follicle in ovaries of women with polycystic ovary syndrome produces more antimüllerian hormone than its counterpart in a normal ovary: an observational crosssectional study［J］. Fertil Steril, 2015, 103(2): 537-541.

［14］Pellatt L, Rice S, Mason HD. Anti-Mullerian hormone and polycystic ovary syndrome: a mountain too high［J］. Reproduction, 2010, 139(5): 825-833.

［15］Yang M, Li J, An Y, et al. Effects of androgen on immunohistochemical localization of androgen receptor and connexin 43 in mouse ovary［J］. Tissue Cell, 2015, 47(5): 526-532.

［16］Tziomalos K, Katsikis I, Papadakis E, et al. Comparison of markers of insulin resistance and circulating androgens between women with polycystic ovary syndrome and women with metabolic syndrome［J］. Hum Reprod, 2013, 28(3): 785-793.

［17］Azziz, R., Carmina E, Dewailly D, et al., Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline［J］. J Clin Endocrinol Metab, 2006, 91(11): 4237-4245.

［18］Alpa ?és M, Luque-Ramírez M, Martínez-García M, et al. Influence of adrenal hyperandrogenism on the clinical and metabolic phenotype of women with polycystic ovary syndrome［J］. Fertil Steril, 2015, 103(3): 795-801.

［19］Qiao J, Feng HL. Extra-and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence［J］. Hum Reprod Update, 2011, 17(1): 17-33.

［20］Goodarzi MO, Carmina E, Azziz R. DHEA, DHEAS and PCOS［J］. J Steroid Biochem Mol Biol, 2015, 145: 213-225.

［21］Dewailly D, Lujan ME, Carmina E, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society［J］. Hum Reprod Update, 2014, 20(3): 334-352.

［22］Catteau-Jonard S, Jamin SP, Leclerc A, et al. Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome［J］. J Clin Endocrinol Metab, 2008, 93(11): 4456-4461.

［23］Walters KA. Role of androgens in normal and pathological ovarian function［J］. Reproduction, 2015, 149(4): R193-218.

［24］Franks S, Hardy K. Aberrant follicle development and anovulation in polycystic ovary syndrome［J］. Ann Endocrinol (Paris), 2010, 71(3): 228-230.

［25］Dewailly D, Catteau-Jonard S, Reyss AC, et al. The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to thefollicular arrest of the polycystic ovary syndrome［J］. Hum Reprod, 2007, 22(6): 1562-1566.

［26］Catteau-Jonard S, Dewailly D. Pathophysiology of polycystic ovary syndrome: the role of hyperandrogenism［J］. Front Horm Res, 2013, 40: 22-27.

［27］Homburg R, Crawford G. The role of AMH in anovulation associated with PCOS: a hypothesis［J］. Hum Reprod, 2014, 29(6): 1117-1121.

［28］Wei D, Shi Y, Li J, et al. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome［J］. Hum Reprod, 2017, 32(2): 354-361.

［29］Huang R, Zheng J, Li S, et al. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome［J］. Acta Obstet Gynecol Scand, 2015, 94(5): 494-500.

［30］Cassar S, Teede HJ, Moran LJ,et al. Polycystic ovary syndrome and anti-Müllerian hormone: role of insulin resistance, androgens, obesity and gonadotrophins［J］. Clin Endocrinol (Oxf), 2014, 81(6): 899-906.

［31］Ruan Y, Ma J, Xie X. Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis［J］. Endocr J, 2012, 59(7): 601-609.

［32］Rashidi B, Azizy L, Najmeddin F, et al. Prevalence of the insulin receptor substrate-1(IRS-1) Gly972Arg and the insulin receptor substrate-2(IRS-2) Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women［J］. J Assist Reprod Genet, 2012, 29(2): 195-201.

［33］Christopoulos P, Mastorakos G, Gazouli M, et al. Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact［J］. Gynecol Endocrinol, 2010, 26(9): 698-703.

［34］Rojas J, Chávez M, Olivar L, et al. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth［J］. Int J Reprod Med, 2014, 2014: 719050.

［35］Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrome［J］. Trends Mol Med, 2006, 12(7): 324-332.

［36］Wu S, Divall S, Nwaopara A, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell［J］. Diabetes, 2014, 63(4): 1270-1282.

［37］Kyaw Tun T, McGowan A, Phelan N, et al. Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome［J］. Int J Endocrinol, 2016, 2016: 9545239.

［38］Moran C, Arriaga M, Arechavaleta-Velasco F, et al. Adrenal androgen excess and body mass index in polycystic ovary syndrome［J］. J Clin Endocrinol Metab, 2015, 100(3): 942-950.

［39］Anderson AD, Solorzano CM, McCartney CR. Childhood obesity and its impact on the development of adolescent PCOS［J］. Semin Reprod Med, 2014, 32(3): 202-213.

［40］Spritzer PM, Lecke SB, Satler F, et al. Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome［J］. Reproduction, 2015, 149(5): R219-R227.

［41］Cui N, Wang H, Wang W, et al. Impact of Body Mass Index on Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection Among Polycystic Ovarian Syndrome Patients［J］. Cell Physiol Biochem, 2016, 39(5): 1723-1734.

［42］Aghadavod E, Zarghami N, Farzadi L, et al. Evaluation of relationship between serum levels of anti-müllerian hormone, androgen, andinsulin resistant with retrieval oocytes in overweight patients with polycystic ovary syndrome［J］. Adv Biomed Res, 2015, 4: 76.

[1]	HUANG Jian-lei CHEN Shu-qiang WANG Ming LI Chen-long MU Jing LIU Dan SUN Hui-jun WANG Xiao-hong. Correlation between follicular fluid metabolic markers and oocyte quality in patients with polycystic ovary syndrome [J]. Acta Anatomica Sinica, 2021, 52(2): 289-294.
[2]	ZHAO Xiao-jin* TIAN Hua-xiang HU Hai-yang HU Feng-xia. Sex differences in the relative length of phalange in rhesus macaques (Macaca Mulatta) from the Taihang Mountains [J]. AAS, 2015, 46(5): 673-678.
[3]	. Influence of experimental cryptorchidism on Leydig cells in adult rats [J]. , 2011, 42(1): 124-0.
[4]	. P>Effects of compound panax notoginseng on the expressions of androgen receptor and c-kit in testicular tissues in formaldehyde rats exposure/P> [J]. , 2010, 41(6): 867-871.
[5]	. Effect of low-dose gossypol acetic acid combined with steroid hormones on the expressions of Cdc25A,cyclin B1 and androgen receptor in adult rat testis [J]. , 2010, 41(03): 435-439.
[6]	. EXPRESSION OF ECTONUCLEOTIDEPYROPHOSPHATASE/PHOSPHODIESTERASE 1 IN HUMAN OVARY AND ITS RELATIONSHIP WITH POLYCYSTIC OVARY SYNDROME [J]. , 2008, 39(4): 552-556.
[7]	. EFFECTS OF ANDROGEN ON LEARNING AND MEMORY ABILITY AND HIPPOCAMPUS NEURONS IN SAMP8 MOUSE [J]. , 2008, 39(3): 365-369.