Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE) on human granulosa cell aromatase activity.
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 1beta-[(3)H]androstenedione and measuring the release of (3)H(2)O.


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.
Younglai
Edward V
EV
Department of Obstetrics & Gynaecology, Reproductive Biology Division, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada. younglai@mcmaster.ca
Holloway
Alison C
AC
Lim
Gareth E
GE
Foster
Warren G
WG
D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*
D007306:Insecticides; D003633:Dichlorodiphenyl Dichloroethylene; D005640:Follicle Stimulating Hormone; D001141:Aromatase