ROLE OF THE ANDROGEN-RECEPTOR GENE IN THE GENESIS OF PREMATURE OVARIAN FAILURE


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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

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