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This Article Full Text Full Text (PDF) All Versions of this Article: 70/1/25    most recent biolreprod.103.019000v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smida, A. D. Articles by Chedrese, J. Search for Related Content PubMed PubMed Citation Articles by Smida, A. D. Articles by Chedrese, J. Agricola Articles by Smida, A. D. Articles by Chedrese, J.

Cadmium Stimulates Transcription of the Cytochrome P450 Side Chain Cleavage Gene in Genetically Modified Stable Porcine Granulosa Cells¹

Toxicology Centre,³ Department of Obstetrics, Gynecology, and Reproductive Sciences,⁴ Department of Veterinary Biomedical Sciences,⁵ University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 0W8 Facultad de Ciencias Veterinarias,⁶ UNCPBA, Tandil, Argentina

We investigated the effects of cadmium (Cd²⁺) on transcription of the cytochrome P450 side chain cleavage (P450scc) gene and on progesterone synthesis in stable granulosa cells. We used the stable porcine granulosa cell line, JC-410, genetically modified to express a luciferase genomic construct carrying 2320 base pairs (bp) of the P450scc gene promoter (P450scc-2320-LUC). A construct containing only the luciferase gene, pOLUC, was used as a promoterless control. At 1 µM, cadmium chloride (CdCl₂) increased transient expression of P450scc-2320-LUC in JC-410 cells by 2.6-fold after 24-h incubation. A similar pattern of stimulation by CdCl₂ was observed in cells transiently transfected with a luciferase genomic construct carrying 100 bp of the P450scc gene promoter P450scc-100-LUC, whereas no stimulation by CdCl₂ was observed in cells transfected with pOLUC. At 0.6, 1, and 2 µM, CdCl₂ stimulated the activity of the P450scc-2320-LUC promoter in a dose-related fashion by 1.58-, 3.19-, and 2.67-fold, respectively, after 24-h incubation. Northern blot analysis showed that CdCl₂ at 0.1, 1, 2, and 3 µM increased P450scc mRNA levels by 3.13-, 1.38-, 1.61-, and 1.57-fold, respectively, after 24-h incubation. After 48-h incubation, CdCl₂ at 0.6, 1, and 2 µM further increased P450scc mRNA levels by 3.43-, 2.08-, and 2.4-fold, respectively. At 1, 2, and 3 µM, CdCl₂ inhibited progesterone synthesis to 0.48-, 0.38-, and 0.29-fold, respectively. After 48-h incubation, CdCl₂ at 0.1 µM stimulated progesterone synthesis by 1.6-fold. We conclude that Cd²⁺ has a dual action in stable porcine granulosa cells: Low concentrations activate, whereas high concentrations inhibit, expression of the P450scc gene and progesterone synthesis. The stimulatory effect of Cd²⁺ appears to be mediated via a cis-acting element located 100 bp upstream of the P450scc gene transcription start site.

¹ Funded by the Canadian Network of Toxicology Centers, Natural Sciences and Engineering Research Council of Canada, Saskatchewan Agricultural Development Fund, J. Murray Research Grant, and Clinical Teaching and Research Grant, College of Medicine, University of Saskatchewan.

² Correspondence: Jorge Chedrese, Department of Obstetrics, Gynecology, and Reproductive Sciences, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, Canada S7N 0W8. FAX: 306 966 8040; chedresj{at}duke.usask.ca

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