Effects of dioxin (2,3,7,8-TCDD) and PCDDs/PCDFs congeners mixture on steroidogenesis in human placenta tissue culture.
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 dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) extracted from fly ash on the placental steroidogenesis. The concentration of all 17 toxic congeners was reported and the toxic equivalent (TEQ) was calculated as a 27.7 micrograms-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 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity the placental cells were cultured either in basal conditions 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 progesterone (P4) secretion suggesting a reduction in the activity of cytochrome P450scc or 3 beta-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.


CONCLUSIONS
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-dioxin (PeCDD) and pentachlorodibenzo-furan (PeCDF) which covered > 50% of the total toxic equivalents (TEQ) present in this mixture.
Augustowska
Katarzyna
K
Laboratory of Physiology and Toxicology of Reproduction, Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland.
Gregoraszczuk
Ewa L
EL
Milewicz
Tomasz
T
Krzysiek
Jozef
J
Grochowalski
Adam
A
Chrzaszcz
Ryszard
R
D002478:Cells, Cultured; D004147:Dioxins / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis* / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D011374:Progesterone; D004958:Estradiol