HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morán, F.M. Articles by Lasley, B.L. Search for Related Content PubMed PubMed Citation Articles by Morán, F.M. Articles by Lasley, B.L. Agricola Articles by Morán, F.M. Articles by Lasley, B.L.

2,3,7,8-Tetrachlorodibenzo-p-Dioxin Decreases Estradiol Production Without Altering the Enzyme Activity of Cytochrome P450 Aromatase of Human Luteinized Granulosa Cells In Vitro¹

^a Institute of Toxicology and Environmental Health, ^b Population Health and Reproduction, ^c California Regional Primate Research Center, University of California-Davis, Davis, California 95616

This study was designed to examine the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on steroid production in human luteinizing granulosa cells (hLGC). TCDD (10 nM) or its solvent was added at the time of changing medium, directly to the cells, every 48 h for 8 days. To test the hypothesis that TCDD reduces estradiol (E₂) synthesis by an effect on cytochrome P450 aromatase, aromatase protein and aromatase activity were evaluated. E₂ decreased without changing either aromatase protein or its enzyme activity, suggesting that the target of toxicity of TCDD is upstream of aromatase in the steroidogenic pathway. When hLGC were incubated in the presence of labeled E₂, no changes in the metabolism of E₂ by treatment were observed. Since TCDD did not change progesterone or 17-hydroxyprogesterone, the inhibition of E₂ synthesis by TCDD would seem not to involve steps such as cholesterol transport. Furthermore, the TCDD effect on E₂ concentration in these cells disappeared in the presence of excess androgens. We conclude that the inhibition of E₂ secretion by TCDD involves intermediate steps, specifically, the provision of androgens for aromatization.

First decision: 6 October 1999.

¹ Supported by NIH ESO 6198, RR 00169, and 1RO1HD36913.

² Correspondence: Bill L. Lasley, Division of Reproductive Biology, Institute of Toxicology and Environmental Health, University of California, Davis, Old Davis Road, One Shields Avenue, Davis, CA 95616-8615. FAX: 530 752 5300; bllasley{at}ucdavis.edu

This article has been cited by other articles:

				Z. Shi, K. E. Valdez, A. Y. Ting, A. Franczak, S. L. Gum, and B. K. Petroff Ovarian Endocrine Disruption Underlies Premature Reproductive Senescence Following Environmentally Relevant Chronic Exposure to the Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Biol Reprod, February 1, 2007; 76(2): 198 - 202. [Abstract] [Full Text] [PDF]

				J. T. Sanderson The Steroid Hormone Biosynthesis Pathway as a Target for Endocrine-Disrupting Chemicals Toxicol. Sci., November 1, 2006; 94(1): 3 - 21. [Abstract] [Full Text] [PDF]

				J. Mutoh, J. Taketoh, K. Okamura, T. Kagawa, T. Ishida, Y. Ishii, and H. Yamada Fetal Pituitary Gonadotropin as an Initial Target of Dioxin in Its Impairment of Cholesterol Transportation and Steroidogenesis in Rats Endocrinology, February 1, 2006; 147(2): 927 - 936. [Abstract] [Full Text] [PDF]

				S. A. Myllymaki, T. E. Haavisto, L. J. S. Brokken, M. Viluksela, J. Toppari, and J. Paranko In Utero and Lactational Exposure to TCDD; Steroidogenic Outcomes Differ in Male and Female Rat Pups Toxicol. Sci., December 1, 2005; 88(2): 534 - 544. [Abstract] [Full Text] [PDF]

				L.-A. Li and P.-W. Wang PCB126 Induces Differential Changes in Androgen, Cortisol, and Aldosterone Biosynthesis in Human Adrenocortical H295R Cells Toxicol. Sci., May 1, 2005; 85(1): 530 - 540. [Abstract] [Full Text] [PDF]

				C. F. Skibola, J. D. Curry, C. VandeVoort, A. Conley, and M. T. Smith Brown Kelp Modulates Endocrine Hormones in Female Sprague-Dawley Rats and in Human Luteinized Granulosa Cells J. Nutr., February 1, 2005; 135(2): 296 - 300. [Abstract] [Full Text] [PDF]

				C.J. Corbin, F.M. Moran, J.D. Vidal, J.J. Ford, T. Wise, S.M. Mapes, V.C. Njar, A.M. Brodie, and A.J. Conley Biochemical Assessment of Limits to Estrogen Synthesis in Porcine Follicles Biol Reprod, August 1, 2003; 69(2): 390 - 397. [Abstract] [Full Text] [PDF]

				F. M. Moran, C. A. VandeVoort, J. W. Overstreet, B. L. Lasley, and A. J. Conley Molecular Target of Endocrine Disruption in Human Luteinizing Granulosa Cells by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Inhibition of Estradiol Secretion Due to Decreased 17{alpha}-Hydroxylase/17,20-Lyase Cytochrome P450 Expression Endocrinology, February 1, 2003; 144(2): 467 - 473. [Abstract] [Full Text] [PDF]

				F.M. Moran, P. Lohstroh, C.A. VandeVoort, J. Chen, J.W. Overstreet, A.J. Conley, and B.L. Lasley Exogenous Steroid Substrate Modifies the Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on Estradiol Production of Human Luteinized Granulosa Cells In Vitro Biol Reprod, January 1, 2003; 68(1): 244 - 251. [Abstract] [Full Text] [PDF]