Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age

Endocrinology

Volumn 154, Issue 1, 2013, Pages 434-445

  Maliqueo, Manuel ^a   Sun, Miao ^b   Johansson, Julia ^a   Benrick, Anna ^a   Labrie, Fernand ^c,d   Svensson, Henrik ^a   Lon̈n, Malin ^a   Duleba, Antoni J ^e   Stener Victorin, Elisabet ^a,b  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b HEILONGJIANG UNIVERSITY OF CHINESE MEDICINE   (China)

^c LAVAL UNIVERSITY   (Canada)

^d AL IMAM MOHAMMAD IBN SAUD ISLAMIC UNIVERSITY IMSIU   (Saudi Arabia)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATASE; CYTOCHROME P450 17; ESTROGEN; FOLLITROPIN; LETROZOLE; LUTEINIZING HORMONE; MESSENGER RNA; PLACEBO;

ADIPOCYTE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANOVULATION; ARTICLE; CELL SIZE; CLINICAL FEATURE; CONTROLLED STUDY; DOSE RESPONSE; FEMALE; GENE EXPRESSION; HYPERANDROGENISM; INGUINAL REGION; INSULIN RESISTANCE; LIPID STORAGE; MESENTERY; NONHUMAN; OVARY CYST; OVARY FOLLICLE ATRESIA; OVARY POLYCYSTIC DISEASE; PHENOTYPE; PREPUBERTY; PRIORITY JOURNAL; RAT; TREATMENT DURATION; WEIGHT GAIN;

ANIMALS; AROMATASE INHIBITORS; FEMALE; NITRILES; POLYCYSTIC OVARY SYNDROME; RATS; RATS, WISTAR; TRIAZOLES;

EID: 84871702645     PISSN: 00137227     EISSN: 19457170     Source Type: Journal    
DOI: 10.1210/en.2012-1693     Document Type: Article

References (67)

1. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R 2011 Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7:219-231
2. Dunaif A 2006 Insulin resistance in women with polycystic ovary syndrome. Fertil Steril 86(Suppl 1):S13-S14
3. Manners̊-Holm L, Leonhardt H, Kullberg J, Jennische E, Odén A, Holm G, Hellström M, Lönn L, Olivecrona G, Stener-Victorǐn E, Lönn M 2011 Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab 96:E304-E311
4. Mannerås-Holm L, Baghaei F, Holm G, Janson PO, Ohlsson C, Lönn M, Stener-Victorǐn E 2011 Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome. J Clin Endocrinol Metab 96:1068-1076
5. Wild RA 2012 Dyslipidemia in PCOS. Steroids 77:295-299
6. de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM 2011 PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis.HumReprod Update 17:495-500
7. Homburg R 2009 Androgen circle of polycystic ovary syndrome. Hum Reprod 24:1548-1555
8. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley Jr WF 1988 Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab 66:165-172 (Pubitemid 18027747)
9. Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss III JF, McAllister JM 2001 The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab 86:5925-5933 (Pubitemid 33152646)
10. Greiner M, Paredes A, Araya V, Lara HE 2005 Role of stress and sympathetic innervation in the development of polycystic ovary syndrome. Endocrine 28:319-324 (Pubitemid 43042731)
11. Faulds G, Rydén M, Ek I, Wahrenberg H, Arner P 2003 Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J Clin Endocrinol Metab 88:2269-2273 (Pubitemid 36549907)
12. Sverrisdttir YB, Mogren T, Kataoka J, Janson PO, Stener-Victorǐn E 2008 Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab 294:E576-E581
13. Simoni M, Tempfer CB, Destenaves B, Fauser BC 2008 Functional genetic polymorphisms and female reproductive disorders. I. Polycystic ovary syndrome and ovarian response. Hum Reprod Update 14:459-484
14. Xita N, Lazaros L, Georgiou I, Tsatsoulis A 2010 CYP19 gene: a genetic modifier of polycystic ovary syndrome phenotype. Fertil Steril 94:250-254
15. Wang H, Li Q, Wang T, Yang G, Wang Y, Zhang X, Sang Q, Wang H, Zhao X, Xing Q, Shi J, He L, Wang L 2011 A common polymorphism in the human aromatase gene alters the risk for polycystic ovary syndrome and modifies aromatase activity in vitro. Mol Hum Reprod 17:386-391
16. Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER 1993 Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci USA 90:11673-11677 (Pubitemid 24008701)
17. Walters KA, Allan CM, Handelsman DJ 2012 Rodent models for human polycystic ovary syndrome. Biol Reprod 86:149, 1-12
18. Mannerås L, Cajander S, Holmäng A, Seleskovic Z, Lystig T, Lönn M, Stener-Victorǐn E 2007 A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 148:3781-3791
19. Keller J, Mandala M, Casson P, Osol G 2011 Endothelial dysfunction in a rat model of PCOS: evidence of increased vasoconstrictor prostanoid activity. Endocrinology 152:4927-4936
20. Alexanderson C, Eriksson E, Stener-Victorǐn E, Lystig T, Gabrielsson B, Lönn M, Holmäng A 2007 Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone. Endocrinology 148:5369-5376
21. Holmäng A, Svedberg J, Jennische E, Björntorp P 1990 Effects of testosterone on muscle insulin sensitivity and morphology in female rats. Am J Physiol 259:E555-E560 (Pubitemid 20340374)
22. Dellapasqua S, Colleoni M 2010 Letrozole. Expert Opin Drug Metab Toxicol 6:251-259
23. Baravalle C, Salvetti NR, Mira GA, Pezzone N, Ortega HH 2006 Microscopic characterization of follicular structures in letrozole-induced polycystic ovarian syndrome in the rat. Arch Med Res 37:830-839 (Pubitemid 44349101)
24. Kafali H, Iriadam M, Ozardali I, Demir N 2004 Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res 35:103-108 (Pubitemid 38316828)
25. Marcondes FK, Bianchi FJ, Tanno AP 2002 Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 62:609-614
26. Consolazio CF, Matoush LR, Nelson RA, Torres JB, Isaac GJ 1963 Environmental temperature and energy expenditures. J Appl Physiol 18:65-68
27. Björnheden T, Jakubowicz B, Levin M, Odén B, Edén S, Sjöström L, Lönn M 2004 Computerized determination of adipocyte size. Obes Res 12:95-105 (Pubitemid 41137492)
28. Mannerås L, Fazliana M, Wan Nazaimoon WM, Lönn M, Gu HF, Ostenson CG, Stener-Victorǐn E 2010 Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome. J Ethnopharmacol 127:346-351
29. Stener-Victorin E, Holm G, Labrie F, Nilsson L, Janson PO, Ohlsson C 2010 Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J Clin Endocrinol Metab 95:810-819
30. Ortega I, Cress AB, Wong DH, Villanueva JA, Sokalska A, Moeller BC, Stanley SD, Duleba AJ 2012 Simvastatin reduces steroidogenesis by inhibiting Cyp17a1 gene expression in rat ovarian theca-interstitial cells. Biol Reprod 86:1-9
31. Livak KJ, Schmittgen TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25:402-408 (Pubitemid 34164012)
32. Corbould A 2008 Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome? Diabetes Metab Res Rev 24:520-532
33. Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L, Chang C, Hung MC 2002 Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci USA 99:13498-13503 (Pubitemid 35215410)
34. Volpi E, Lieberman SA, Ferrer DM, Gilkison CR, Rasmussen BB, Nagamani M, Urban RJ 2005 The relationships between testosterone, body composition, and insulin resistance: a lesson from a case of extreme hyperandrogenism. Diabetes Care 28:429-432 (Pubitemid 40170955)
35. Escobar-Morreale HF, San Millán JL 2007 Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 18:266-272 (Pubitemid 47332217)
36. James DE, Jenkins AB, Kraegen EW 1985 Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats. Am J Physiol 248:E567-E574 (Pubitemid 15018375)
37. Corbould A 2007 Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol 192:585-594 (Pubitemid 46455961)
38. Veilleux A, Caron-Jobin M, Noël S, Laberge PY, Tchernof A 2011 Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes 60:1504-1511
39. Skurk T, Alberti-Huber C, Herder C, Hauner H 2007 Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92:1023-1033 (Pubitemid 46465679)
40. Moran LJ, Misso ML, Wild RA, Norman RJ 2010 Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 16:347-363
41. Watanobe H, Suda T 1999 A detailed study on the role of sex steroid milieu in determining plasma leptin concentrations in adult male and female rats. Biochem Biophys Res Commun 259:56-59 (Pubitemid 29263993)
42. Desai BN, Maharjan RH, Nampoothiri LP 2012 Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat model. Pharmacognosy Res 4:109-115
43. Walters KA, AllanCM,Handelsman DJ 2008 Androgen actions and the ovary. Biol Reprod 78:380-389 (Pubitemid 351416471)
44. Billig H, Furuta I, Hsueh AJ 1993 Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology 133:2204-2212 (Pubitemid 23324728)
45. Yang JL, Zhang CP, Li L, Huang L, Ji SY, Lu CL, Fan CH, Cai H, Ren Y, Hu ZY, Gao F, Liu YX 2010 Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis. Endocrinology 151:774-782
46. Nestler JE, Jakubowicz DJ 1996 Decreases in ovarian cytochrome P450c17 α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 335:617-623 (Pubitemid 26277951)
47. Taniguchi F, Couse JF, Rodriguez KF, Emmen JM, Poirier D, Korach KS 2007 Estrogen receptor-α mediates an intraovarian negative feedback loop on thecal cell steroidogenesis via modulation of Cyp17a1 (cytochrome P450, steroid 17α-hydroxylase/17,20 lyase) expression. FASEB J 21:586-595 (Pubitemid 46213505)
48. Zurvarra FM, Salvetti NR, Mason JI, Velazquez MM, Alfaro NS, Ortega HH 2009 Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat. Reprod Fertil Dev 21:827-839
49. Foecking EM, McDevitt MA, Acosta-Martínez M, Horton TH, Levine JE 2008 Neuroendocrine consequences of androgen excess in female rodents. Horm Behav 53:673-692
50. Andrews WW, Ojeda SR 1981 A quantitative analysis of the maturation of steroid negative feedbacks controlling gonadotropin release in the female rat: the infantile-juvenile periods, transition from an androgenic to a predominantly estrogenic control. Endocrinology 108:1313-1320 (Pubitemid 11079153)
51. Blank SK, McCartney CR, Helm KD, Marshall JC 2007 Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty. Semin Reprod Med 25:352-359 (Pubitemid 47339159)
52. D'Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS 2005 Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 280:35983-35991 (Pubitemid 41633867)
53. Song D, Arikawa E, Galipeau DM, Yeh JN, Battell ML, Yuen VG, McNeill JH 2005 Chronic estrogen treatment modifies insulin-induced insulin resistance and hypertension in ovariectomized rats. Am J Hypertens 18:1189-1194 (Pubitemid 41337971)
54. Bryzgalova G, Gao H, Ahren B, Zierath JR, Galuska D, Steiler TL, Dahlman-Wright K, Nilsson S, Gustafsson JA, Efendic S, Khan A 2006 Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver. Diabetologia 49:588-597 (Pubitemid 43277883)
55. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS 2000 Increased adipose tissue in male and female estrogen receptor-α knockout mice. Proc Natl Acad Sci USA 97:12729-12734
56. Jones ME, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S, Simpson ER 2000 Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA 97:12735-12740
57. Misso ML, Murata Y, Boon WC, Jones ME, Britt KL, Simpson ER 2003 Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse. Endocrinology 144:1474-1480 (Pubitemid 36428489)
58. Takeda K, Toda K, Saibara T, Nakagawa M, Saika K, Onishi T, Sugiura T, Shizuta Y 2003 Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. J Endocrinol 176:237-246 (Pubitemid 36284816)
59. Britt KL, Drummond AE, Cox VA, Dyson M, Wreford NG, Jones ME, Simpson ER, Findlay JK 2000 An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene. Endocrinology 141:2614-2623 (Pubitemid 32273173)
60. Toda K, Takeda K, Okada T, Akira S, Saibara T, Kaname T, Yamamura K, Onishi S, Shizuta Y 2001 Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17α-oestradiol. J Endocrinol 170:99-111 (Pubitemid 32677571)
61. Yonden Z, Aydin M, Alcin E, Kelestemur MH, Kutlu S, Yilmaz B 2009 Effects of letrozole on bone biomarkers and femur fracture in female rats. J Physiol Biochem 65:267-275
62. Couse JF, Yates MM, Walker VR, Korach KS 2003 Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERα but not ERα. Mol Endocrinol 17:1039-1053 (Pubitemid 36683712)
63. Fisher CR, Graves KH, Parlow AF, Simpson ER 1998 Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci USA 95:6965-6970 (Pubitemid 28278090)
64. Bronstein J, Tawdekar S, Liu Y, Pawelczak M, David R, Shah B 2011 Age of onset of polycystic ovarian syndrome in girls may be earlier than previously thought. J Pediatr Adolesc Gynecol 24:15-20
65. Sir-Petermann T, Codner E, Pérez V, Echiburú B, Maliqueo M, Ladrón de Guevara A, Preisler J, Crisosto N, Sánchez F, Cassorla F, Bhasin S 2009 Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 94:1923-1930
66. Naessen T, Kushnir MM, Chaika A, Nosenko J, Mogilevkina I, Rockwood AL, Carlstrom K, Bergquist J, Kirilovas D 2010 Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry. Fertil Steril 94:2228-2233
67. Wang L, Li S, Zhao A, Tao T, Mao X, Zhang P, Liu W 2012 The expression of sex steroid synthesis and inactivation enzymes in subcutaneous adipose tissue of PCOS patients. J Steroid Biochem Mol Biol 132:120-126