Hum. Reprod. Advance Access originally published online on April 7, 2004
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Human Reproduction, Vol. 19, No. 5, 1089-1093,
May 2004
© 2004 European Society of Human Reproduction and Embryology
Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE) on human granulosa cell aromatase activity
Department of Obstetrics & Gynaecology, Reproductive Biology Division, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada
1 To whom correspondence should be addressed at: Department of Obstetrics & Gynaecology, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5. e-mail: younglai{at}mcmaster.ca
BACKGROUND: 1,1-Dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE, DDE), a metabolite of DDT, is a persistent hormonally active environmental toxicant which has been found in human serum and follicular fluid. The objective of this study was to investigate the interaction between FSH and ppDDE on aromatase activity in primary cultures of human granulosa cells. METHODS: Granulosa cells were obtained at the time of oocyte retrieval for IVF procedures and cultured in defined medium containing FSH and environmentally relevant concentrations of DDE. Aromatase activity was measured by incubating the cells with 1
-[3H]androstenedione and measuring the release of 3H2O. RESULTS: The granulosa cell response to FSH was highly dependent on the basal level of aromatase activity (r = –0.703, P = 0.001, n = 17) with the highest activity occurring at low basal levels of aromatase activity. Enzyme activity was significantly stimulated at 100 ng DDE/ml. A synergistic effect on aromatizing activity was observed when cells were co-cultured with DDE and FSH. CONCLUSIONS: Concentrations of DDE similar to those present in human follicular fluid enhance basal and FSH-stimulated granulosa cell aromatizing enzyme activity.
Key words: aromatase/DDE/FSH/synergism
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