DDT and its metabolite DDE alter steroid hormone secretion in human term placental explants by regulation of aromatase activity.
Placental explants were used to compare the effects of two isomers of DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane), p,p'-DDT and o,p'-DDT and their metabolites p,p'-DDE and o,p'-DDE (1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene) on steroid hormone secretion (estradiol (E2) and progesterone (P4)). Explants were treated with 1, 10, 100ng/ml or 1microg/ml of each compound for 24h. We found that all investigated compounds at all doses caused reductions of estradiol secretion. Moreover, it was shown that the inhibition of estradiol secretion was due to direct action on aromatase activity. Twenty-four-hour exposure to p,p'-DDE, o,p'-DDT or o,p'-DDE at doses of 100ng/ml or 1microg/ml increased P4 secretion, suggesting that these compounds act on P450scc. The fluorometric assay confirmed that all investigated compounds inhibited aromatase activity at a concentration of 100ng/ml. Our findings suggest that by decreasing estradiol secretion with concomitant stimulation of progesterone secretion, DDT could be a factor that influences the outcome of pregnancy.
Wójtowicz
Anna K
AK
Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Krakow, Poland. wojtow@zuk.iz.uj.edu.pl
Milewicz
Tomasz
T
Gregoraszczuk
Ewa Ł
EŁ
D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000378:metabolism / Q000633:toxicity*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003634:DDT / Q000378:metabolism / Q000633:toxicity*; D003687:Dehydroepiandrosterone / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007536:Isomerism; D010575:Pesticides / Q000378:metabolism / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D046509:Tissue Culture Techniques
D047072:Aromatase Inhibitors; D010575:Pesticides; D003687:Dehydroepiandrosterone; D011374:Progesterone; D003633:Dichlorodiphenyl Dichloroethylene; D004958:Estradiol; D003634:DDT; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme