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Hum. Reprod. Advance Access published online on April 7, 2004
Human Reproduction, doi:10.1093/humrep/deh252
© 2004 by European Society of Human Reproduction and Embryology
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Received June 24, 2003
Accepted March 10, 2004

Article

Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE) on human granulosa cell aromatase activity

Edward V. Younglai 1*, Alison C. Holloway 1, Gareth E. Lim 1, and Warren G. Foster 1

1 Department of Obstetrics & Gynaecology, Reproductive Biology Division, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: younglai{at}mcmaster.ca.


  Abstract

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{beta}-[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: Key words: aromatase/DDE/FSH/synergism


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