N D Shaw1, S S Srouji, C K Welt, K H Cox, J H Fox, J M Adams, P M Sluss, J E Hall. 1. 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.
Abstract
CONTEXT: 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. DESIGN: The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study. MAIN OUTCOME MEASURES: 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: E E Marsh; N D Shaw; K M Klingman; T O Tiamfook-Morgan; M A Yialamas; P M Sluss; J E Hall Journal: J Clin Endocrinol Metab Date: 2011-08-17 Impact factor: 5.958
Authors: G M Lambert-Messerlian; J E Hall; P M Sluss; A E Taylor; K A Martin; N P Groome; W F Crowley; A L Schneyer Journal: J Clin Endocrinol Metab Date: 1994-07 Impact factor: 5.958
Authors: Laura Pellatt; Suman Rice; Nafi Dilaver; Amira Heshri; Raymond Galea; Mark Brincat; Kristy Brown; Evan R Simpson; Helen D Mason Journal: Fertil Steril Date: 2011-09-13 Impact factor: 7.329
Authors: Radia Boudjenah; Denise Molina-Gomes; Antoine Torre; Marianne Bergere; Marc Bailly; Florence Boitrelle; Stéphane Taieb; Robert Wainer; Mohamed Benahmed; Philippe de Mazancourt; Jacqueline Selva; François Vialard Journal: PLoS One Date: 2012-06-11 Impact factor: 3.240
Authors: Sonya M Schuh-Huerta; Nicholas A Johnson; Mitchell P Rosen; Barbara Sternfeld; Marcelle I Cedars; Renee A Reijo Pera Journal: Hum Reprod Date: 2011-11-24 Impact factor: 6.918
Authors: Osman A Dufailu; Afrakoma Afriyie-Asante; Bernard Gyan; David Adu Kwabena; Helena Yeboah; Frank Ntiakoh; Meshach Asare-Werehene Journal: J Ovarian Res Date: 2021-05-21 Impact factor: 4.234
Authors: Song-Yi Park; Julie R Palmer; Lynn Rosenberg; Christopher A Haiman; Elisa V Bandera; Traci N Bethea; Melissa A Troester; Emma Viscidi; Laurence N Kolonel; Andrew F Olshan; Christine B Ambrosone Journal: Carcinogenesis Date: 2016-04-07 Impact factor: 4.944
Authors: N D Shaw; S S Srouji; C K Welt; K H Cox; J H Fox; J A Adams; P M Sluss; J E Hall Journal: J Clin Endocrinol Metab Date: 2015-06-30 Impact factor: 5.958
Authors: Raina D Pang; Mariel S Bello; Madalyn M Liautaud; Andrea H Weinberger; Adam M Leventhal Journal: Nicotine Tob Res Date: 2019-07-17 Impact factor: 4.244
Authors: Liisa A M Galea; Karyn M Frick; Elizabeth Hampson; Farida Sohrabji; Elena Choleris Journal: Neurosci Biobehav Rev Date: 2016-03-31 Impact factor: 8.989
Authors: Erica E Marsh; Lia A Bernardi; Marissa L Steinberg; Peter J de Chavez; Jenny A Visser; Mercedes R Carnethon; Donna D Baird Journal: Fertil Steril Date: 2016-04-23 Impact factor: 7.329
Authors: Kristen R Moore; Meena Tomar; David M Umbach; Scott E Gygax; David W Hilbert; Donna D Baird Journal: Sex Transm Dis Date: 2021-11-01 Impact factor: 3.868
Authors: Jelonia T Rumph; Victoria R Stephens; Joanie L Martin; LaKendria K Brown; Portia L Thomas; Ayorinde Cooley; Kevin G Osteen; Kaylon L Bruner-Tran Journal: Int J Environ Res Public Health Date: 2022-01-23 Impact factor: 3.390