Younglai Edward V, Holloway Alison C, Lim Gareth E, Foster Warren G
Department of Obstetrics & Gynaecology, Reproductive Biology Division, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada.
Hum Reprod. 2004 May;19(5):1089-93. doi: 10.1093/humrep/deh252. Epub 2004 Apr 7.
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.
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.
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.
Concentrations of DDE similar to those present in human follicular fluid enhance basal and FSH-stimulated granulosa cell aromatizing enzyme activity.
1,1-二氯-2,2-双（对氯苯基）乙烯（P,P'-滴滴滴，DDE）是滴滴涕的一种代谢产物，是一种具有激素活性的持久性环境毒物，已在人体血清和卵泡液中被发现。本研究的目的是调查卵泡刺激素（FSH）和P,P'-滴滴滴对人颗粒细胞原代培养物中芳香化酶活性的相互作用。
在进行体外受精（IVF）程序取卵时获取颗粒细胞，并在含有FSH和环境相关浓度滴滴涕的特定培养基中培养。通过将细胞与1β-[³H]雄烯二酮孵育并测量³H₂O的释放来测定芳香化酶活性。
颗粒细胞对FSH的反应高度依赖于芳香化酶活性的基础水平（r = -0.703，P = 0.001，n = 17），在芳香化酶活性基础水平较低时活性最高。在100 ng DDE/ml时酶活性受到显著刺激。当细胞与DDE和FSH共同培养时，观察到对芳香化活性有协同作用。
与人体卵泡液中存在的浓度相似的滴滴涕浓度可增强基础的和FSH刺激的颗粒细胞芳香化酶活性。
