UW-Madison School of Pharmacy

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Richard E Peterson, Ph.D.

Professor
Charles M. Johnson Chair

 

 

 


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant which elicits a wide range of toxic responses. The developing male rat reproductive system is 100 times more sensitive to TCDD than is its adult counterpart. In utero and lactational exposure to a single low dose delays testis descent and preputial separation, decreases testis, epididymis, and accessory sex organ weights, and decreases daily sperm production, epididymal sperm reserves, and ejaculated sperm numbers throughout development. The mechanism underlying the spectrum of toxic responses elicited by TCDD is poorly understood. TCDD binds the aryl hydrocarbon receptor (AhR), which translocates to the nucleus and dimerizes with the AhR nuclear translocator (ARNT). This complex, a ligand-activated transcription factor, binds to enhancer elements (DREs) in the 5' regulatory region of genes and activates transcription. Although none of the TCDD-responsive genes identified to date have been directly linked to toxicity, it is thought that induction or repression of transcription of genes which have not yet been identified may play a key role in eliciting toxic responses. To better understand the mechanism by which TCDD selectively impairs the developing male reproductive system, we are characterizing the ontogeny and distribution of the AhR and ARNT within this organ system. In addition, we are working to identify genes that are transcriptionally modulated by in utero and lactational TCDD exposure in the prostate and epididymis, two organs which are particularly sensitive to this treatment. The identification of a TCDD-responsive gene(s) with known function may provide insight into the mechanism by which TCDD affects growth and/or function of the prostate, epididymis, and perhaps other organs as well. Novel genes will require characterization before mechanistic hypotheses can be formulated.

Background: Richard received his B.S. degree (1967) from the University of Wisconsin-Madison and his Ph.D. degree in pharmacology (1972) from the Marquette University School of Medicine (now the Medical College of Wisconsin). He joined the faculties of the School of Pharmacy and the Environmental Toxicology Center at the University of Wisconsin-Madison in 1975. He currently serves as Deputy Director of the NIEHS Center for Developmental and Molecular Toxicology. His research interests are in toxicology.

Professional Interests: Toxicology

Education:

  • B.S. 1967 - University of Wisconsin-Madison
  • Ph.D. 1972 Pharmacology - Marquette University School of Medicine

Highlighted Publications:
  • Bar-Ilan, O., Louis, K., Yang, S., Pedersen, J.A., Hamers, R.J., Peterson, R.E., and Heideman, W.: TiO2 nanoparticles produce phototoxicity in the developing zebrafish. Nanotoxicol, in press.
  • Zhou, Y., Cashman, T., Nevis, K., Obregon, P., Carney, S.A., Liu, Y., Gu, A., Mosimann, C., Sondalle, S., Peterson, R.E., Heideman, W., Burns, C.E., and Burns, C.G.: Ventricular and outflow tract morphogenesis from the zebrafish second heart field requires LTBP3 mediated-TGFβ signaling. Nature 474: 645-648, 2011.
  • Kubota, A., Stegeman, J.J., Woodin, B., Iwanaga, T., Harano, R., Peterson, R.E., Hiraga, T., and Teraoka, H.: Role of zebrafish P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2. Toxicol. Appl. Pharmacol., in press.
  • Yoshioka, W., Peterson, R.E., and Tohyama, C.: Molecular targets that link dioxin exposure and toxicity phenotypes. J. Steroid Biochem. Mol. Biol., in press.
  • Teraoka, H., Ogawa, A., Kubota, A., Stegeman, J.J., Peterson, R.E., and Hiraga, T.: Malformation of specific brain blood vessels caused by TCDD activation of AHR2/ARNT1 signaling in developing zebrafish. Aquat. Toxicol. 99: 241-247, 2010.
  • Zhang, J., Lanham, K.A., Peterson, R.E., Heideman, W., and Li. L.: Characterization of the adult zebrafish cardiac proteome using online pH gradient SCX-RP 2DLC coupled with ESI tandem mass spectrometry. J. Sep. Sci. 33 (10): 1462-1471, 2010.
  • Allgeier, S.H., Lin, T.-M., Moore, R.W., Vezina, C.M., and Peterson, R.E.: Androgenic regulation of ventral epithelial bud number and pattern in mouse urogenital sinus. Dev. Dyn. 239: 373-385, 2010.
  • Vezina, C.M., Hardin, H.A., Moore, R.W., Allgeier, S.H., and Peterson, R.E.: 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits fibroblast growth factor 10-induced prostatic bud formation in mouse urogenital sinus. Toxicol. Sci. 113: 198-206, 2009.
  • Wiecinski, P. N., Heiden, T. C. K., Metz, K. M., Mangham, A. N., Hamers, R. J., Heideman, W., et al.: Developmental toxicity of oxidatively degraded quantum dots. Geochimica Et Cosmochimica Acta, 73 (13), 1437, 2009.
  • Allgeier, S.H., Vezina, C.M., Silverstone, A.E., Mukai, M., Gavalchin, J., Lin, T.-M., Cooke, P.S., and Peterson, R.E.: Estrogen signaling is not required for prostatic bud patterning or for its disruption by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Tox. Appl. Pharmacol. 239: 80-86, 2009.
  • King Heiden, T.C., Spitsbergen, J., Heideman, W., and Peterson, R.E.: Persistent adverse effects on health and reproduction caused by exposure of zebrafish to 2,3,7,8-tetrachlorodibenzo-p-dioxin during early development and gonad differentiation. Toxicol. Sci. 109: 75-87, 2009.
  • Fritz, W.A., Lin, T.-M., Safe, S., Moore, R.W., and Peterson, R.E.: The selective aryl hydrocarbon receptor modulator 6-methyl-1,3,8-trichlorodibenzofuran inhibits prostate tumor metastasis in TRAMP mice. Biochem. Pharmacol. 77: 1151-1160, 2009.
  • King Heiden, T.C., Wiecinski, P.N., Mangham, A.N., Metz, K.M., Nesbit, D., Pedersen, J.A., Hamers, R.J., Heideman, W., and Peterson, R.E.: Quantum dot nanotoxicity assessment using the zebrafish embryo. Environ. Sci. Technol. 43: 1605-1611, 2009.
  • Hill, A.J., Heiden, T.C., Heideman, W., and Peterson, R.E.: Potential roles of Arnt2 in zebrafish larval development. Zebrafish 6: 79-91, 2009.
  • Vezina, C.M., Lin, T.-M., and Peterson, R.E.: AHR signaling in prostate growth, morphogenesis, and disease. Biochem. Pharmacol. 77: 566-576, 2009.
  • Teraoka, H., Furuya, M., Dong, W., Yamazaki, K., Mori, C., Harada, Y., Peterson, R.E., and Hiraga, T.: Role of the cyclooxygenase 2-thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo. Toxicol. Appl. Pharmacol. 234: 33-40, 2009.