Polychlorinated biphenyls (PCB 153 and PCB 126) action on conversion of 20-hydroxylated cholesterol to progesterone, androstenedione to testosterone, and testosterone to estradiol 17beta.
To look for one of the possible mechanisms of action we investigated the effect of two congeners of polychlorinated biphenyls (PCB153 as one of the most prominent environmental contaminants and PCB 126 as one of the most toxic contaminants similar to dioxin) on the cellular conversion of steroid precursors as an indicator for enzyme activity (20-hydroxylated cholesterol to progesterone for P450 (scc,) androstendione to testosterone for 17-beta-HSD, and testosterone to estradiol for P450 (arom)). The net synthesis and secretion of particular steroids was used as the indicator of enzyme activity. Co-culture of pig granulosa and theca cells isolated from small (SF) and large (LF) follicles, was carried out in medium M199 supplemented with 100 ng/ml of PCB 153 or 100 pg/ml of PCB 126. The inhibitory action of both PCB 126 and PCB 153 on progesterone secretion by cells isolated from SF and LF follicles was reversed in the presence of 20-hydroxylated cholesterol. The addition of PCB 126 into the culture medium caused a decrease in testosterone secretion by cells isolated from both SF and LF and this effect was reversed in the presence of androstendione. The inhibitory action of PCB 153 on testosterone secretion was reversed by the addition of androstendione to the culture medium in SF, while it caused even additional stimulatory action on cells collected from LF. No effect of PCB 126 and statistically significant decrease in estradiol secretion by cells collected from SF under the influence of PCB153 was observed. The inhibitory effect of PCB 153 was reversed when the culture was supplemented with testosterone. The opposite effect of both tested congeners on estradiol secretion in both basal and testosterone supplemented culture was seen in LF. PCB 126 increased it while PCB 153 decreased both, the basal and testosterone-stimulated estradiol secretion. In conclusion, the presented results suggest that the effect of both PCBs on steroid secretion observed in an early stage of the follicular phase of the estrus cycle is due to the inhibition of cholesterol mobilisation and thus insufficient substrate availability for hormone synthesis. On the contrary, in large preovulatory follicles inhibition of testosterone secretion is due to their action on 17-beta-HSD while stimulatory or inhibitory action on estradiol secretion is the result of their action on P450 aromatase activity.
Wójtowicz
A K
AK
Laboratory of Physiology and Toxicology of Reproduction, Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Kraków, Poland. wojtow@zuk.iz.uj.edu.pl
Goch
M
M
Gregoraszczuk
E L
EL
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D013552:Swine; D013799:Theca Cells / Q000166:cytology / Q000502:physiology*
D004965:Estrogen Antagonists; D012739:Gonadal Steroid Hormones; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D001141:Aromatase; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl