Professor of Medicine and of Physiology
Dr. St. Germain received a B.S. degree in Chemical Engineering from Louisiana State University in 1972 and subsequently attended the Johns Hopkins University School of Medicine where he received the M.D. degree in 1976. He completed his clinical training in Internal Medicine and Endocrinology at University Hospitals of Cleveland in 1980, and then undertook a postdoctoral research fellowship in the Departments of Medicine and Physiology at Dartmouth Medical School. He was appointed to the faculty of Dartmouth Medical School in 1984.
The overall objective of Dr. St. Germain's research is to determine the physiological parameters and biochemical mechanisms that regulate the metabolism and action of thyroid hormones (TH). An additional major focus of his research is to develop a better understanding of the functional consequences and importance of TH metabolism through the use of transgenic animal models developed by he and his colleagues.
Because the effects of TH are mediated primarily through the interaction of 3,5,3'-triiodothyronine (T3) with the nuclear thyroid hormone receptor, the cellular factors regulating T3 production and degradation are of considerable physiologic importance. The iodothyronine deiodinases enzymes that convert thyroxine (T4) to T3 and 3,3',5'-triiodothyronine (rT3) in extrathyroidal tissues are selenium-containing, thiol-dependent proteins. The regulation of these enzymes is hormone- and developmentally-dependent and tissue-specific and involves complex alterations in enzyme activation and inactivation. The three deiodinase enzymes have proved difficult to purify and, thus, until recently, little was known about their biochemical characteristics. However, efforts at isolating cDNAs for these enzymes have been successful and have provided tools for the development of several transgenic strains of mice that either overexpress or underexpress one or more of the deiodinases. The phenotypic characterization and manipulation of these transgenic mouse lines is now a major focus of Dr. St. Germain's research.
Through these studies, new insights are being provided into the role of TH and the deiodinases in brain development, reproductive function, growth, thermogenesis and regulation of the thyroid axis. Because Dr. St. Germain holds a joint appointment in Medicine and Physiology, he has a close working relationship with members of both the basic science and clinical faculties. This gives him and his associates the opportunity of participating in a broad range of academic endeavors.
St. Germain, D. L., Schwartzman, R., Croteau, W., Kanamori, A., Wang, Z., Brown, D. D., and Galton, V. A. 1994. A thyroid hormone regulated gene in Xenopus laevis encodes a type III 5-deiodinase. Proc. Natl. Acad. Sci. USA 91:7767-7771. Correction: Proc. Natl. Acad. Sci. USA 91:11282, 1994.
Croteau, W., Whittemore, S. L., Schneider, M. J., and St. Germain, D. L. 1995. Cloning and expression of a cDNA for a mammalian type III iodothyronine deiodinase. J. Biol. Chem. 270:16569-16575.
Davey, J. C., Becker, K. B., Schneider, M. J., St. Germain, D. L., and Galton,V. A. 1995. Cloning of a cDNA for the type II iodothyronine deiodinase. J. Biol. Chem. 270: 26786-26789.
Croteau, W., Davey, J. C., Galton, V. A., St. Germain, D. L. 1996. Cloning of the mammalian type II iodothyronine deiodinase: a selenoprotein differentially expressed and regulated in the human brain and other tissues. J. Clin. Invest. 98:405-417.
Pallud, S., Lennon, A.-M., Ramauge, M., Gavaret, J.-M., Croteau, W., Pierre, M., Courtin, F., and St. Germain, D. L. 1997. Expression of the type II iodothyronine deiodinase selenoprotein in cultured rat astrocytes. J. Biol. Chem. 272:18104-18110.
Burmeister, L. A., Pachucki, J., and St. Germain, D. L. 1997. Thyroid hormones inhibit type II 5'-deiodinase in the rat cerebral cortex by both pre- and post-translational mechanisms. Endocrinology 138:5231-5237.Schneider, M. J., Fiering, S. N., Pallud, S. E., Parlow, A. F., St. Germain, D. L., and Galton, V. A. 2001. Targeted expression of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol. Endocrinol. 15:2137-2148.
Hernandez, A., Fiering, S., Martinez, E., Galton, V. A., and St. Germain, D. L. 2002. The gene locus encoding the iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts. Endocrinology. 143:4483-4486.
Hernandez, A. and St. Germain, D. L. 2003. Activity and response to serum of the mammalian thyroid hormone deiodinase type 3 promoter: identification of a conserved enhancer. Mol. Cell. Endocrinol. 206:23-32.
Hernandez, A., Martinez, M. E,. Croteau, W., and St. Germain, D. L. 2004. Complex organization and structure of sense and antisense transcripts expressed from the DIO3 gene imprinted locus. Genomics 83:413-424.
[8/9/05]