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Polymorphisms of the Androgen Receptor Gene and the Estrogen Receptor ß Gene Are Associated with Androgen Levels in Women¹

Department of Pharmacology (L.W., M.H., M.J., E.E.), Institute of Heart and Lung Disease (F.B., R.R., G.H., P.B.), and Institute of Clinical Neuroscience, Section of Psychiatry (M.L.), Goteborg University, SE 405 30 Goteborg, Sweden

Address all correspondence and requests for reprints to: Dr. Lars Westberg, Department of Pharmacology, Goteborg University, P.O. Box 431, DE 405 30 Goteborg, Sweden. E-mail: lars.westberg{at}pharm.gu.se

Abstract

To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor (ER), and ERß on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER gene, and the CA repeat polymorphism of the ERß gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3-androstanediol glucuronide, 17ß-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ERß gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ERß gene, respectively.

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