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High Aromatase Expression in Uterine Leiomyoma Tissues of African-American Women

Division of Reproductive Biology Research (H.I., S.R., M.D., S.E.B.), Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, and Biostatistics Core Facility (A.W.R.), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611; Department of Obstetrics and Gynecology (T.K., M.I.), Kanazawa University Graduate School of Medicine, Takaramachi, Kanazawa-shi, Ishikawa-ken 920-8641, Japan; and Department of Reproductive Medicine (H.U., M.S.), Graduate School of Medicine, Chiba University, Chuo-ku, Chiba-shi 260-8670, Japan

Address all correspondence and requests for reprints to: Serdar E. Bulun, M.D., Professor and Chief, Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, 303 E. Superior Street, Suite 4-123, Chicago, Illinois 60611. E-mail: s-bulun{at}northwestern.edu.

Context: Symptomatic uterine leiomyoma is associated with irregular uterine bleeding, anemia, and recurrent pregnancy loss. African-American women develop uterine leiomyomas at an earlier age and with higher frequency compared with Caucasian-American women or other races; however, the underlying mechanism for this discrepancy is unknown.

Objective: Our objective was to determine whether gene targets of emerging leiomyoma therapeutics such as aromatase inhibitors and antiprogestins, which reduce tumor size and symptoms, are differentially expressed in tissues of African-American (n = 31), Caucasian-American (n = 34), and Japanese women (n = 36).

Results: We found strikingly higher aromatase mRNA levels in leiomyoma compared with adjacent myometrium in African-American (83 fold), Caucasian-American (38 fold), and Japanese women (33 fold). Among the four major promoters that regulate aromatase expression in leiomyoma, the proximal promoter II accounted for higher aromatase mRNA levels in tissues from African-American women. Estrogen receptor subtype mRNA levels were significantly, and 1.8- to 2.6-fold, higher in leiomyoma compared with adjacent myometrium in all groups, whereas leiomyoma estrogen receptor subtype β mRNA levels were significantly elevated only in Japanese women. Leiomyoma progesterone receptor mRNA levels were significantly higher in Japanese women compared with African-American or Caucasian-American women.

Conclusions: Leiomyoma tissues from African-American women contained the highest level of aromatase expression, which may result in elevated tissue concentrations of estrogen, and account for the higher prevalence and earlier incidence. Analysis of leiomyoma tissue for biomarkers may predict the response to hormonal treatments such as aromatase inhibitors.

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