title: Evidence that increased ovarian aromatase activity and expression account for higher estradiol levels in African American compared with Caucasian women.
abstract: BACKGROUND
  Serum estradiol levels are significantly higher across the menstrual cycle in African American (AAW) compared with Caucasian women (CW) in the presence of similar FSH levels, yet the mechanism underlying this disparity is unknown.
  
  
  OBJECTIVE
  The objective of the study was to determine whether higher estradiol levels in AAW are due to increased granulosa cell aromatase mRNA expression and activity.
  
  
  METHODS
  The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle.
  
  
  METHODS
  Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study.
  
  
  METHODS
  Hormone levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and FSH receptor mRNA expression in granulosa cells were measured.
  
  
  RESULTS
  AAW had higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median (interquartile range); P < .001] and estrone [76.9 (36.6-173.4) vs 28.8 (22.5-42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had lower FF androstenedione to estrone (7 ± 1.8 vs 15.8 ± 4.1; mean ± SE; P = .04) and T to estradiol (0.01 ± 0.002 vs 0.02 ± 0.005; P = .03) ratios, indicating enhanced ovarian aromatase activity. There was a 5-fold increase in granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH levels were not different in AAW and CW.
  
  
  CONCLUSIONS
  Increased ovarian aromatase mRNA expression, higher FF estradiol levels, and decreased FF androgen to estrogen ratios in AAW compared with CW provide compelling evidence that racial differences in ovarian aromatase activity contribute to higher levels of estradiol in AAW across the menstrual cycle. The absence of differences in FSH, FSH receptor expression, and AMH suggest that population-specific genetic variation in CYP19, the gene encoding aromatase, or in factors affecting its expression should be sought.
authors.affiliation: Reproductive Endocrine Unit (N.D.S., S.S.S., C.K.W., K.H.C., J.M.A., P.M.S., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston Massachusetts 02114; and Division of Endocrinology (N.D.S.), Children's Hospital Boston, and Center for Infertility and Reproductive Surgery (S.S.S., J.H.F.), Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: N D
authors.initials: ND
authors.lastname: Shaw
authors.forename: S S
authors.initials: SS
authors.lastname: Srouji
authors.forename: C K
authors.initials: CK
authors.lastname: Welt
authors.forename: K H
authors.initials: KH
authors.lastname: Cox
authors.forename: J H
authors.initials: JH
authors.lastname: Fox
authors.forename: J M
authors.initials: JM
authors.lastname: Adams
authors.forename: P M
authors.initials: PM
authors.lastname: Sluss
authors.forename: J E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism*; D004958:Estradiol / Q000097:blood*; D005260:Female; D015571:Follicular Fluid / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006107:Granulosa Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism; D006080:Ovarian Follicle / Q000201:enzymology*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D004958:Estradiol; D001141:Aromatase