Effects of low-dose endocrine disruptors on neonatal prostatic development

• Project/Area Number: 17510046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Hiroshima University
• Principal Investigator: FUJIMOTO Nariaki Hiroshima University, RIRBM, Associate Professor (40243612)
• Co-Investigator(Kenkyū-buntansha): 北村 繁幸 広島大学, 大学院・医歯薬学総合研究科, 助教授 (40136057)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: mouse / prostate / prostatic proteins / estrogen receptor promoter / endocrine disruptors / benzophenones / brominated flame retardants / 発生異常

Research Abstract

1. Identification of prostatic secreted proteins in mice: Major secreted proteins from the ventral (VP), dorso-lateral (DLP) and anterior prostate (AP) of mice were identified by means of two-dimensional gel electrophoresis followed by MALDI-TOF mass spectrometric analysis. The measurement of newly identified prostate proteins should contribute to an understanding of developmental interference of endocrine disrupting chemicals.
2. In vivo function of the 5' flanking region of mouse estrogen receptor (ER)β gene: It has been postulated that ER has an important role in development of the prostate gland, so that regulation of ER is critical for understanding toxicological effects of endocrine disruptors in prostate development. We examined the in vivo promoter activity of 5'f region of the ERβ gene in transgenic mice with the lacZ reporter. About 2.2 kbps of the proximal 5'f region of ERβ was cloned and inserted into reporter plasmids. Quantitative measurement of mRNA showed that lacZ was expressed only in the testis, in which sertoli were confirmed to be lacZ-positive, but not in the prostate. The study suggests that the 5'f region is able to direct testis-specific expression, but is not itself sufficient to determine the expression in other organs.
3. Androgen activity of benzophenone and bromine-based flame retardants: Using the androgen responsive gene reporter assay and in vivo prostate assay, androgenic activities of benzophenones (BPs), used as UV stabilizers, and brominated flame retardants, were examined. Interestingly, 2,4,4'-triOH-BP were found to be androgenic (with partially anti-androgenic activity) as well as estrogenic. This chemical could potentially disrupt the neonatal development of the prostate by both hormonal activities.

Research Products

• [Journal Article] Quantitative determination of lobe specificity of mrna expression of and rogen-dependent genes in the rat prostate gland (2007)
  • Author(s): Suzuki., T., Fujimoto., N., Kitamura, S., Ohta, S.
  • Journal Title: Endocr.J. 54 Pages: 123-132
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Invivo function of the 5'flanking region of mouse estrogen receptor beta gene (2007)
  • Author(s): Fujimoto, N., Nakajima, O., Suzuki, T., Kitamura, S., Ohta, S.
  • Journal Title: J.Steroid Biochem.Mol.Biol. 105 Pages: 57-62
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Quantitative determination of lobe specificity of mrna expression of androgen-dependent genes in the rat prostate gland. (2007)
  • Author(s): Suzuki., T., Fujimoto., N., Kitamura, S., Ohta, S.
  • Journal Title: Endocr. J. 54 Pages: 123-132
  • NAID: 10019479578
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Quantitative determination of lobe specificity of mRNA expression of androgen-dependent genes in the rat prostate gland. (2007)
  • Author(s): Suzuki, T.
  • Journal Title: Endocr. J. 54 Pages: 123-132
• [Journal Article] PSPCl,NONO,and SFPQ are expressed in mouse Sertoli cells and may function as coregulators of androgen receptor-mediated transcription (2006)
  • Author(s): Kuwahara, S., Ikei, A., Taguchi, Y., Tabuchi, Y., Fujimoto, N., Obinata, M., Uesugi, S., Kurihara, Y.
  • Journal Title: Biol.Reprod. 75 Pages: 352-359
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of prostatic-secreted proteins in mice by mass spectrometric analysis and evaluation of lobe-specific and androgen-dependent mRNA expression (2006)
  • Author(s): Fujimoto, N., Akimoto, Y., Suzuki, T., Kitamura, S., Ohta, S.
  • Journal Title: J.Endo. 190 Pages: 793-803
  • NAID: 120000878100
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PSPCI, NONO, and SFPQ are expressed in mouse Sertoli cells and may function as coregulators of androgen receptor-mediated transcription. (2006)
  • Author(s): Kuwahara, S., Ikei, A., Taguchi, Y., Tabuchi, Y., Fujimoto, N., Obinata, M., Uesugi, S., Kurihara, Y.
  • Journal Title: Biol. Reprod. 75 Pages: 352-359
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of prostatic-secreted proteins in mice by mass spectrometric analysis and evaluation of lobe-specific and androgen-dependent mRNA expression. (2006)
  • Author(s): Fujimoto, N., Akimoto, Y., Suzuki, T., Kitamura, S., Ohta, S.
  • Journal Title: J. Endo. 190 Pages: 793-803
  • NAID: 120000878100
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vivo function of the 5'flanking region of mouse estrogen receptor beta gene. (2006)
  • Author(s): Fujimoto, N., Nakajima, 0., Suzuki, T., Kitamura, S., Ohta, S.
  • Journal Title: J. Steroid Biochem. Mol. Biol. 105 Pages: 57-62
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Endocrine Disruption by organophosphate and Carbamate pesticides In : R. C. Gupta(ed.) Toxicology of organophosphate and carbamate compounds (2006)
  • Author(s): Kitaniura, S., Sugihara, K., Fujimoto, N.
  • Journal Title: Elsevier Academic Press, London Pages: 481-494
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of prostatic-secreted proteins in mice by mass spectrometric analysis and evaluation of lobe-specific and androgen-dependent mRNA expression. (2006)
  • Author(s): Fujimoto, N.
  • Journal Title: J. Endo. 190 Pages: 793-803
  • NAID: 120000878100
• [Journal Article] PSPC1, NONO, and SFPQ are expressed in mouse-Sertoli cells and may function as coregulators of androgen receptor-mediated transcription. (2006)
  • Author(s): Kuwahara, S.
  • Journal Title: Biol. Reprod. 75 Pages: 352-359
• [Journal Article] Estimation of aldehyde oxidase activity in vivo from conversion ratio of N1-methylnicotinamide to pyridones, and intraspecies variation of the enzyme activity in rats (2006)
  • Author(s): Sugihara, K.
  • Journal Title: Drug Metabolism and Dispostition 34・2 Pages: 208-212
• [Journal Article] Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds (2005)
  • Author(s): Kitamura, S., Suzuki, T., Sauoh, S., Kohta, R., Jinno, N., Sugihara, K., Yoshihara, S., Fujimoto, N., Watanabe, H., Ohta, S.
  • Journal Title: Toxicol.Sci 84 Pages: 1-12
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens (2005)
  • Author(s): Suzuki, T., Kitamura, S., Khota, R., Sugihara, K., Fujimoto, N., Ohta, S.
  • Journal Title: Toxicol.Appl.Pharmacol. 203 Pages: 9-17
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture (2005)
  • Author(s): Kitamura, S., Jinno, N., Suzuki, T., Sugihara, K., Ohta, S., Kuroki, H., Fujimoto, N.
  • Journal Title: Toxicology 208 Pages: 377-387
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Anti-thyroidhormonal activity of tetrabromobisphenol A,aflame retardant,and related compounds:affinity to the mammalian thyroid hormone receptor,and effect on tadpole (2005)
  • Author(s): Kitamura, S., Kato, T., Iida, M., Jinno, N., Suzuki, T, Ohta, S., Fujimoto, N., Hanada, H., Kashiwagi, K., Kashiwagi, A.
  • Journal Title: Life Sci. 76 Pages: 1589-1601
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cloning and characterization of the 5'-flanking region of the rat estrogen receptor βgene (2005)
  • Author(s): Fujimoto, N., Asano, K., Usui, T., Honda, H., Kitamura, S.
  • Journal Title: J.Steroid Biochem.Mol.Biol. 94 Pages: 15-21
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Metabolism of the alpha,beta-unsaturated ketones,chalcone and trans-4-phenyl-3-buten-2-one,by rat liver microsomes and estrogenic activity of the metabolites (2005)
  • Author(s): Kohno Y., Kitamura S., Sanoh S., Sugihara K., Fujimoto N., Ohta S.
  • Journal Title: Drug Metab.Dispos. 33 Pages: 1115-23
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds. Toxicol. Sci., 84, 1-12(2005) (2005)
  • Author(s): Kitamura, S., Suzuki, T., Sanoh, S., Kohta, R., Jinno, N., Sugihara, K., Yoshihara, S., Fujimoto, N., Watanabe, H., Ohta, S.
  • Journal Title: Toxicol. Sci. 84 Pages: 1-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens. (2005)
  • Author(s): Suzuki, T., Kitamura, S., Khota, R., Sugihara, K., Fujimoto, N., Ohta, S.
  • Journal Title: Toxicol. Appi. Pharmacol. 203 Pages: 9-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture. (2005)
  • Author(s): Kitamura, S., Jinno, N., Suzuki, T., Sugihara, K., Ohta, S., Kuroki, H., Fujimoto, N.
  • Journal Title: Toxicology 208 Pages: 377-387
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds : affmity to the mammalian thyroid hormone receptor, and effect on tadpole. (2005)
  • Author(s): Kitamura, S., Kato, T., lida, M., Jinno, N., Suzuki, T, Ohta, S., Fujimoto, N., Hanada, H., Kashiwagi, K., Kashiwagi, A.
  • Journal Title: Life Sci. 76 Pages: 1589-1601
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cloning and characterization of the 5'-flanking region of the rat estrogen receptor β gene (2005)
  • Author(s): Fujimoto, N., Asano, K., Usui, T., Honda, H., Kitamura, S.
  • Journal Title: J. Steroid Biochem. Mol. Biol. 94 Pages: 15-21
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Metabolism of the alpha, beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites. (2005)
  • Author(s): Kohno Y., Kitamura S., Sanoh S., Sugihara K., Fujimoto N., Ohta S.
  • Journal Title: Drug Metab. Dispos. 33 Pages: 1115-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metaholites (2005)
  • Author(s): Kohno Y.
  • Journal Title: Drug Metabolism and Dispostition 33・8 Pages: 1115-1123
• [Journal Article] Production of superoxide radical in reductive metabolism of a synthetic food-coloring agent, indigocarmine, and related compounds (2005)
  • Author(s): Kohno Y.
  • Journal Title: Life Science 77・6 Pages: 601-614
• [Journal Article] Involvement of molybdenum hydroxylases in reductive metabolism of nitro polycyclic aromatic hydrocarbons in mammalian skin (2005)
  • Author(s): Ueda,. O.
  • Journal Title: Drug Metabolism and Dispostition 33・9 Pages: 1312-1318
• [Book] Endocrine Disruption by organophosphate and Carbamate pesticides In : Toxicology of organophosphate and carbamate compounds(R.C.Gupta(ed.) (2006)
  • Author(s): Kitamura S.
  • Total Pages: 14
  • Publisher: Elsevier Academic Press, London
• [Book] Endocrine Disruption by organophosphate and Carbamate pesticides In:R.C.Gupta(ed.)Toxicology of organophosphate and carbamate compounds (2005)
  • Author(s): Kitamura, S., Sugihara, K., Fujimoto, N.
  • Publisher: Elsevier Academic Press,London
  • Description: 「研究成果報告書概要(和文)」より