There are two major research programs active in the laboratory, both related to thyroid hormones. First, we are interested in understanding the functional organization of neurons in the brain that control pituitary-thyroid activity. These neurons synthesize Thyrotropin-Releasing Hormone (TRH). This endocrine axis plays an important role in the regulation of growth and development and of basal metabolism. Currently, we are using both physiological and molecular approaches to understand the functional organization of hypophysiotropic thyrotropin-releasing hormone (TRH) neurons.

R. Thomas Zoeller   Molecular Mechanisms of Thyroid Hormone Action on Early Cortical Development; Endocrine Disruptors For additional information about our research and the people involved in performing the work, please visit our Home Page.

Second, we are interested in the role of thyroid hormone in guiding brain development. To address this, we are cloning novel thyroid hormone-regulated genes in the fetal brain. In addition, there are a number of clinically relevant factors that may interfere with thyroid hormone action during development, including environmental contaminants (e.g., PCBs), and ethanol. We are using the genes we have found to be thyroid hormone-regulated as probes to test whether these factors do in fact disrupt thyroid hormone action in the fetus and in the adult.

Publications:

Zoeller, R.T. 2001. Polychlorinated Biphenyls as Disruptors of Thyroid Hormone Action. In:Recent Advances in the Environmental Toxicology and Health Effects of PCBs. (In press) .

Dowling, A.L.S., Iannacone, E.I., and Zoeller, R.T. 2001. Maternal Hypothyroidism Selectively Affects the Expression of Neuroendocrine-Specific Protein-A mRNA in the Fetal Rat Brain. Endocrinology 142(1): 390-399.

Zoeller, R.T. and Crofton, K.M. 2000. Thyroid Hormone Action in Fetal Brain Development and Potential for Disruption by Environmental Chemicals. NeuroToxicology 21(6): 935-945.

Myers, J.P., Krimsky, S., and Zoeller, R.T. 2000. Endocrine Disruptors: A Controversy in Science and Policy. Session III Summary and Research Needs. NeuroToxicology 21:1-2.

Dowling, A.L.S. and Zoeller, R.T. 2000. Thyroid Hormone of Maternal Origin Regulates the Expression of RC3/Neurogranin mRNA in the Fetal Rat Brain. Molecular Brain Research 82: 126-132.

Dowling, A.L.S., Martz, G.U., Leonard, J.L., Zoeller, R.T. 2000. Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Specific Gene Expression in Fetal Rat Brain. Journal of Neuroscience 20(6): 2255-2265.

Slikker, W. Jr., Zoeller, R.T. 2000. Hot New Topics in Developmental Neurotoxicology - Novel and Changing Perspectives: Session X Summary and Research Needs. NeuroToxicology 21(1-2): 279-280.

Zoeller, R.T., Dowling, A.L.S., and Vas, A.A. 2000. Developmental Exposure to Polychlorinated Biphenyls Exerts Thyroid Hormone-Like Effects on the Expression of RC3/Neurogranin and Myelin Basic Protein Messenger Ribonucleic Acids in the Developing Rat Brain. Endocrinology 141(1): 181-189.

Bigsby, R., Chapin, R.E., Daston, G.P., Davis, B.J., Gorski, J., Gray, L.E., Howdeshell, K.L.,vom Saal, F.S., and Zoeller, R.T. 1999. Evaluating the Effects of Endocrine Disruptors on Endocrine Function during Development. Environ Health Perspect. 107(suppl 4): 613-618.

Zoeller R, Fletcher D, Martz G, Dowling A, Yang J, Christie S and Crofton K (1998) Perinatal exposure to polychlorinated biphenyls increases circulating levels of T4, and TSH, and affects the expression of multiple genes in the brain of 200 day-old rats. Thyroid 8 (Suppl 1): S-65.

Kim CK, Giberson PK, Yu W, Zoeller RT, Weinberg J (1998) Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses to chronic cold stress in rats. Alcohol: Clin Exp Res 23: 301-310.

Scott HC, Sun GY, Zoeller RT (1998) Prenatal Ethanol Exposure Selectively Reduces the Alpha-1 Thyroid Hormone Receptor in Fetal Rat. Alcohol Clin Exp Res 22:2111-2117.

Sun D, Swaffield JC, Johnston SA, Milligan CE, Zoeller RT, Schwartz LM (1997) Identification of a phylogenetically conserved Sug1 CAD family member that is differentially expressed in the mouse nervous system. J Neurobiol 33: 877-890.

Albers HE, Zoeller RT, Huhman KL (1997) Application of in situ hybridization to the study of rhythmic neural systems. In: Molecular Regulation of Arousal States, Lydic R, ed., CRC Press.

Lowry CA, Richardson CF, Zoeller RT, Miller LJ, Muske LE, Moore FL (1997) Neuroanatomical distribution of vasotocin in a urodele amphibian (Taricha granulosa) revealed by immunohistochemical and in situ hybridization techniques. J Comp Neurol 385:43-70.

Zoeller RT, Fletcher DL, Butnariu O, Lowry C, Moore FL (1997) N-ethylmaleimide (NEM) can significantly improve in situ hybridization results using ³⁵S-labeled oligodeoxynucleotide or complementary RNA probes. J Histochem Cytochem 45: 1035-1041.

Dowling ALS, Yang J, Leonard J, Zoeller RT (1997) Identification of thyroid hormone regulated genes in the developing rat brain. Thyroid 7 (Suppl 1): S-114.

Zoeller RT, Fletcher DL, Simonyi A, Rudeen PK (1996) Chronic ethanol treatment reduces the responsiveness of the hypothalamic-pituitary-thyroid axis to central stimulation. Alcohol Clin Exp Res 20: 954-960.

Dowling ALS, Leonard J, Zoeller RT (1996) Thyroid hormone regulated genes in the developing rat brain. Soc Neurosci Abs 12: 1220.

Zhang SX, Zhang J-P, Fletcher DL, Zoeller RT, Sun GY (1995) In situ hybridization of mRNA expression for IP3 receptor and IP3-3-kinase in rat brain after transient focal cerebral ischemia. Mol Brain Res 32: 252-260.

Zoeller RT, Simonyi A, Butnariu O, Fletcher DL, Rudeen PK, McCrone SL, Petersen SL (1995) Effects of acute ethanol on the hypothalamic-pituitary-thyroid axis. Endocrine 3: 39-47.

Sun GY, Lin TA, Wixom P, Zoeller RT et al. (1993) Effects of focal cerebral ischemia on expression and activity of inositol 1,4,5-trisphosphate 3-kinase in rat cortex. Ann NY Acad Sci 679: 382-387.

Zoeller RT, Kabeer N, Albers HE (1993) Molecular Mechanisms of Signal Integration in Hypothalamic Neurons. Am Zool 32: 244-254.

Earlier publications:

Mason AJ, Hayflick JS, Zoeller RT, Young III WS, Phillips HS, Nicolics K, Seeburg PH (1986) A deletion truncating the GnRH gene is responsible for hypogonadism in the hpg mouse. Science 234: 1366-1371.

Koller KJ, Wolff RS, Warden MK, Zoeller RT (1987) Thyroid hormones regulate thyrotropin-releasing hormone mRNA levels in the paraventricular nucleus. Proc Natl Acad Sci USA 84: 7329-7333.

Young III WS, Zoeller RT (1987) Neuroendocrine gene expression in the hypothalamus: in situ hybridization studies. Cell Mol Neurobiol 7: 353-366.

Zoeller RT, Seeburg PH, Young III WS (1988) In situ hybridization histochemistry for messenger RNA encoding gonadotropin-releasing hormone (GnRH): effect of estrogen on cellular levels of GnRH mRNA in the organum vasculosum of the lamina terminalis. Endocrinology 22: 2570-2577.

Miller M, Zoeller RT, Dorsa DM (1988) Distribution of vasopressin mRNA-containing neurons in the bed nucleus of the stria terminalis of male rats. Neurosci Lett 94: 264-268.

Zoeller RT, Wolff RS, Koller KJ (1988) Thyroid hormone regulation of messenger ribonucleic acid encoding thyrotropin (TSH)-releasing hormone is independent of the pituitary gland and TSH. Mol Endocrinol 2: 353-366.

Wray S, Zoeller RT, Gainer H (1989) Differential effects of estrogen on LHRH gene expression in slice-explant cultures prepared from specific rat forebrain regions. Mol Endocrinol 3:1197-1206.

Albers HE, Liou SY, Ferris CF, Stopa EG, Zoeller RT (1990) Neurochemistry of Circadian Timing. In: The Suprachiasmatic Nucleus: The Mind's Clock, Klein DC, Moore RY, Reppert SM, eds., New York: Oxford University Press.

Zoeller RT, Kabeer N, Albers HE (1990) Cold exposure elevates cellular levels of messenger ribonucleic acid encoding thyrotropin-releasing hormone in paraventricular nucleus despite elevated levels of thyroid hormones. Endocrinology 127: 2955-2962.

Albers HE, Liou SY, Stopa EG, Zoeller RT (1990) Interaction of co-localized neuropeptides: functional significance in the circadian timing system. J Neurosci 11: 846-851.

Selmanoff M, Shu C, Petersen SL, Barraclough CA, Zoeller RT (1991) Single cell levels of hypothalamic messenger ribonucleic acid encoding luteinizing hormone-releasing hormone in intact, castrated, and hyperprolactinemic male rats. Endocrinology 128: 459-466.

Zoeller RT, Broyles B, Earley J, Anderson ER, Albers HE (1992) Cellular levels of mRNAs encoding vasoactive intestinal peptide (VIP) and gastrin-releasing peptide (GRP) exhibit different 24-hour rhythms in neurons of the suprachiasmatic nucleus. J Neuroendocrinol 4: 119-124.

Zoeller RT, Rudeen PK (1992) Ethanol blocks the cold-induced increase in thyrotropin-releasing hormone mRNA in paraventricular nuclei but not the cold-induced increase in thyrotropin. Mol Brain Res 13: 321-330.

Dolan DR, Nichols MF, Bhend E, Schadt JC, Zoeller RT (1992) Cold- and Ethanol-induced hypothermia reduces cellular levels of mRNA encoding thyrotropin releasing-hormone (TRH) in neurons of the preoptic area. Mol Cell Neurosci 3: 425-432.

Albers HE, Liou S-Y, Stopa EG, Zoeller RT (1992) Neurotransmitter colocalization and circadian rhythms. Progr Brain Res 92: 289-307.

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