ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis
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ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis Patrícia IS Pinto1, Pratap B Singh2, João B Condeça1, Helena R Teodósio1, Deborah M Power1 and Adelino VM Canário*1 Address: 1Centro de Ciências do Mar, CIMAR-Laboratório Associado, University of Algarve, Faro, Portugal and 2Departmentof Zoology, T.D. College, Jaunpur-222002, India Email: Patrícia IS Pinto - [email protected]; Pratap B Singh - [email protected]; João B Condeça - [email protected]; Helena R Teodósio - [email protected]; Deborah M Power - [email protected]; Adelino VM Canário* - [email protected] * Corresponding author
Published: 27 December 2006 Reproductive Biology and Endocrinology 2006, 4:67
doi:10.1186/1477-7827-4-67
Received: 08 October 2006 Accepted: 27 December 2006
This article is available from: http://www.rbej.com/content/4/1/67 © 2006 Pinto et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: ICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus). Methods: Three independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus) or sea bream received intra-peritoneal implants containing estradiol17 beta (E2), ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream. Results: E2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 downregulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2. Conclusion: These results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but i
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