ROLE OF THE ANDROGEN-RECEPTOR GENE IN THE GENESIS OF PREMATURE OVARIAN FAILURE
- Authors: TABEYEVA G.I1, MARCHENKO L.A1, KARSELADZE A.I2, BUTAREVA L.A1, STROGANOVA A.M2
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Affiliations:
- Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
- N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
- Issue: No 6 (2011)
- Pages: 36-41
- Section: Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/246523
- ID: 246523
Cite item
Abstract
Objective. To evaluate the androgen-receptor (AR) gene in ovarian tissues and its association with the production of androgens themselves and to analyze the length of CAG-repeat in the AR gene in patients with premature ovarian failure (POF) and in healthy women. Subjects and methods. One hundred and eighteen women with POF were examined. Twenty intraoperative ovarian biopsy specimens from patients with POF served as a material for fluorescence in situ hybridization (FISH) analysis. Ten ovarian tissue specimens from women who had died during emergencies at less than 40 years of age (mean 28.4±6.3 years) were used as a control. DNA samples from 83 healthy women living in the European part of Russia were analyzed as a population control of AR gene CAG repeat length. Nine reproductive-age healthy women with preserved menstrual rhythm were a control group to estimate the levels of testosterone-estradiol binding globulin, testosterone, and free androgen index. Results. There was a clear tendency for shorter AR gene CAG repeat lengths in patients with POF. The FISH analysis of the ovarian biopsy specimens from the patients with POF showed a change (amplif ication) in the AR gene in almost every three (30%) women with POF while no changes were found in the ovarian biopsy specimens from the women with preserved ovarian function (a control group). Conclusion. The AR gene amplification detected in ovarian tissues in almost every three patients with POF allows one to consider that along with other molecular genetic, autoimmune, and infectious causes, increased AR expression in the presence of a hypoandrogenic state plays a certain role in the basis of this pathology. Our findings permit premature ovarian failure to be considered to result from impaired androgen signaling.
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About the authors
G. I TABEYEVA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
Email: g_tabeeva@oparina4.ru
L. A MARCHENKO
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
A. I KARSELADZE
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
L. A BUTAREVA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
A. M STROGANOVA
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
References
- Габибуллаева З.Г. Клинико-генетическая характеристика больных с преждевременной недостаточностью яичников: Дис.. канд. мед. наук. — М., 2008.
- Aranda A., Pasqual A. Nuclear hormone receptors and gene expression // Physiol. Rev. — 2001. — Vol. 81. — P. 1269— 1304.
- Farnsworth W.E. Roles of estrogen and SHBG in prostate phisiology // Prostate. — 1996. — Vol. 28. — P. 17—23.
- Febbo P.O., Kantoff P.W. Androgen receptor polymorphism and cancer prostate risk // Prostate cancer. Biology, genetics, and the new therapeutics. — 2001. — P. 95—110.
- Gordon N.A., Chamberlain N.L., Flomerfelt F.A. et al. A cell-specific and selective effect on transactivation by the androgen receptor // Exp. Cell. Res. — 1995. — Vol. 217. — P. 368—377.
- Gregory C.W., Hamil K.G., Kim D. et al. Androgen receptor expression in androgen independent prostate cancer is associated with increased expression of androgen regulated genes // Cancer Res. — 1998. — Vol. 58. — P. 5718—5724.
- He B., Wilson E.M. Electrostatic modulation in steroid receptor recruitment of LXXLF and FXXLF motifs // Mol. Cell. Biol. — 2003. — Vol. 23. — P. 2135—2150.
- Heinlein C.A., Chang C. Androgen receptor coregulators: an overview // Endocr. Rev. — 2002. — Vol. 23. — P. 175—200.
- Hickey T., Chandy A., Norman R.J. The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome // J. Clin. Endocrin. Metab. — 2002. — Vol. 87. — P. 161—165.
- Hippakka R.A., Liao S. Molecular mechanism of androgen action // Trends Endocrinol. Metab. — 1998. — Vol. 9. — P. 317—324.
- Kuo P.L., Huang S.C., Chang L.W. et al. Association of extremely skewed X-chromosome inactivation with Taiwanese women presenting with recurrent pregnancy loss // J. Formos. Med. Assoc. — 2008. — Vol. 107. — P. 308—343.
- Mora G.R., Tindall D.J. Activation of androgen receptor // Prostate cancer. biology, genetics and the new therapeutics. — 2001. — P. 219—239.
- Pasternoster S.F., Brockman S.R., McClure R.F. et al. A new method to extract nuclei from paraffin-embedded tissue to study lymphomas using interphase fluorescence in situ hybridization // Am. J. Path. — 2002. — Vol. 160, № 6. — P. 1967—1972.
- Sadar M. Androgen independent induction of prostate specific antigen gene expression via cross talk between the androgen receptor and protein kinase A signal transduction pathways // J. Biol. Chem. — 1999. — Vol. 274. — P. 7777—7783.
- Sato K., Uehara S., Hashiyada M. et al. Genetic significance of skewed X- chromosome inactivation in premature ovarian failure // Am. J. Med. Genet. — 2004. — Vol. 130. — P. 240—244.
- Sugawa F., Wada Y., Maruyama C. et al. Premature ovarian failure and androgen receptor gene CAG repeat lengths weighted by X chromosome inactivation patterns. // Fertil. and Steril. — 2009. — Vol. 92. — P. 649—652.
- Visakorpi T., Hyytinen E., Koivisto P. et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer // Nat. Genet. — 1995. — Vol. 9. — P. 401—406.
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