effects of dioxin (2,3,7,8-tcdd) and pcdds/pcdfs congeners mixture on steroidogenesis in human...

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11 ENDOCRINE REGULATIONS, VOL. 37, 1119, 2003 EFFECTS OF DIOXIN (2,3,7,8-TCDD) AND PCDDs/PCDFs CONGENERS MIXTURE ON STEROIDOGENESIS IN HUMAN PLACENTA TISSUE CULTURE KATARZYNA AUGUSTOWSKA, EWA L GREGORASZCZUK,TOMASZ MILEWICZ 1 , JOZEF KRZYSIEK 1 , ADAM GROCHOWALSKI 2 , RYSZARD CHRZASZCZ 2 Laboratory of Physiology and Toxicology of Reproduction, Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland; 2 Department of Endocrinology and Fertility, Collegium Medicum, Jagiellonian University, Krakow, Poland; Department of Chemistry, Krakow, University of Technology, Krakow, Poland E-mail: [email protected]¿.uj.edu.pl Objective. The aim was to compare the direct effect of most toxic 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) as well as of naturally occurring congener mixture of polychlorinated dibenzo- dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) extracted from fly ash on the pla- cental steroidogenesis. The concentration of all 17 toxic congeners was reported and the toxic equivalent (TEQ) was calculated as a 27.7 µg-TEQ/kg of fly ash. Methods. Placental cotyledons were harvested immediately after expulsion of placenta. The cells were prepared according to KLIMAN et al. (1986). To examine TCDD and PCDDs/PCDFs mixture action on cytochrome P450 side change cleavage enzyme (P450 scc) and 3β-hydroxys- teroid dehydrogenase (3β-HSD) activity the placental cells were cultured either in basal condi- tions or with the addition of 25-hydroxycholesterol (25-OH) or pregnenolone (P5). Results. TCDD in all doses used decreased basal P4 secretion, while did not show any effect on 25-hydroxycholesterol (25-OH) and pregnenolone (P5) supplemented cultures. In all variants of culture PCDDs/PCDFs mixture was without effect on basal and substrate supplemented proges- terone (P4) secretion suggesting a reduction in the activity of cytochrome P450 scc or 3β-HSD. To examine TCDD and PCDDs/PCDFs mixture action on aromatase cytochrom P450 (P450 arom) activity the placental cells were cultured in basal condition or with the addition of dehydroepi- androsterone (DHEA) or testosterone (T). Significant increase of estradiol secretion under the influence of TCDD in DHEA and T supplemented cultures suggests its action on the activity of P450 arom. Conclusion. The discrepancy found between the action of pure TCDD and dioxin mixture on placental steroids secretion is possibly due to an additional effect of pentachlorodibenzo-p-diox- in (PeCDD) and pentachlorodibenzo-furan (PeCDF) which covered >50 % of the total toxic equivalents (TEQ) present in this mixture. Key words: TCDD PCDDs/PCDFs mixture Human placenta Hormonal status 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds elicit a diverse spectrum of toxic responses. As these compounds are lipophylic, they are not easily metabolized and thus any environmen- tal exposure of living organisms results in their ac- cumulation in adipose tissue and thus in bioconcen- tration in the body via food chain. Additionally, they are able to pass through the human placenta (KOPPE et al. 1992). Taking into account the fat solubility of these compounds and the maternal origin of 10 to 20

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