Professor of Physiology
Dr. Galton received her B.Sc. in physiology from the University of London in 1955. Her ancillary subjects were chemistry and physics. From 1955 to 1958 she was a Ph.D. student and Research Assistant at the National Institute for Medical Research in London under Dr. R. Pitt-Rivers, F.R.S., and Sir Charles Harrington, F.R.S. She received her Ph.D. in biochemistry from the University of London in 1958. From 1959-1961 she was a Milton Research fellow at Harvard Medical School. She joined the Physiology Department at Dartmouth as an instructor in 1961 and since 1975 has been a Professor of Physiology.
The long-term goal of Dr. Galton's research is to elucidate the mechanisms of action of thyroid hormones at the molecular level through a study of the relationships among hormone metabolism, hormone receptor interactions and hormone action in both developing and adult mammals. Current studies are concerned with the critical roles played by the deiodinases, enzymes which either activate (D1 and D2) thyroxine (T4) by converting it to its metabolically more active derivative 3,5,3'-triiodothyronine (T3), or inactivate (D3) both T4 and T3 by converting them to inactive derivatives. After cloning the cDNAs for the D2 and D3 from Rana catesbeiana, Dr Galton’s group has shown that differential expression of these enzymes is essential for coordinated metamorphosis of the frog.
The roles of D1, D2 and D3 in mammals in regulating thyroid function are now being assessed. The general hypothesis is that the D1 and the D2 provide for tissue specific adaptations of intracellular T3 production in response to endogenous or environmental threats to thyroid hormone homeostasis. This hypothesis is being tested using genetically altered mouse models that are deficient in one or more of the deiodinases. We have created a D1-deficient (D1KO) mouse, a D2-deficient (D2KO) mouse, and a D1/D2-deficient (D1/D2KO) mouse. All three models are viable and have no gross physiological or behavioral abnormalities. Their detailed phenotypes continue to be assessed.
Thyroid hormone (TH) is essential for normal brain development and TH deficiency in humans leads to mental retardation, deafness and ataxia. We hypothesize that TH
Nutritional deprivation and severe systemic illness present significant, and at times life-threatening challenges to humans and other animal species. Such conditions prompt a complex systemic hormonal response designed to cope with the threat to health. The thyroid axis is intimately involved in regulating energy balance,heart activity, brain function and a host of other metabolic processes. The deiodinases have been implicated in the adaptation of this hormonal system to the stresses of fasting and illness. The deiodinase-deficient mice are being used to define the mechanisms by which the hypothalamic/pituitary/thyroid axis responds to fasting and illness and the clinical consequences of this adaptation.
homeostasis in the developing brain is both cell-type and region specific and is regulated by a complex and dynamic system of TH deiodinases and transporters whose expression levels change during the developmental period. The deiodinase-deficient mice and mice deficient in the TH transporter MCT8 are being used to define their roles in TH homeostasis in brain.
Galton. V.A., Martinez, E., Hernandez, A., St. Germain, E.A., Bates, J.M., St. Germain, D.L. The type 2 iodothyronine deiodinase is expressed in the rat uterus and induced during pregnancy. Endocrinology 142: 2123-2128, 2001
Schneider, M.J., Fiering, S.N., Pallud, S.E., Parlow,A.F., St. Germain, D.L., Galton, V.A. Targeted disruption of the type 2 selenodeiodinase gene (dio2) results in a phenotype of pituitary resistance to thyroxine. Mol Endocrinol. 15: 2137-2148, 2001
Galton, V.A. Physiological Roles of the Deiodinases. Hot Thyroidology, #2 May, 2003 (on-line Journal of the European Thyroid Association)
Wasco, E.C., Martinez, E., Grant, K.S., St.Germain, E.A., St.Germain, D.L., Galton, V.A. Determinants of iodothyronine deiodinase activities in rodent uterus. Endocrinology 114: 4253-4261, 2003.Ng, L., Goodyear,R.J. Woods, C.A., Schneider, M.J., Richardson, G.P., Kelley, M.K., St.Germain, D.L., Galton, V.A., Forrest, D. Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proc. Soc. Natl. Acad. Sci. USA. 101, 3474-3479. 2004.
Galton,V.A. The Roles of the Iodothyronine Deiodinases in Mammalian Development. Thyroid, 15: 823-834, 2005.
St. Germain , D.L., Hernandez, A., Schneider, M.J., Galton. V.A. Insights into the role of deiodinases from studies of genetically modified animals. Thyroid 15: 905-916, 2005.
Schneider, M.J., Fiering, S.N., Thai, B., Wu, S-Y., St. Germain, E., Parlow, A.F., St. Germain, D.L., Galton, V.A. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 147: 580-589, 2006.
Galton, V.A.,, Wood, E.T., St. Germain, E.A., Withrow, C-A., Aldrich, G.,. St. Germain, G.M., Clark,A.S.. St Germain, D.L. Thyroid Hormone Homeostasis and Action in the Type 2 Deiodinase-deficient Brain during Development. Endocrinology, 148: 3080-3088, 2007.
[8/20/08]