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Comparative Medicine
Dr. Thomas Register

Thomas C. Register, PhD

Associate Professor of Pathology (Comparative Medicine)
Tel: (336) 716-1557
Fax: (336) 716-1515
register@wfubmc.edu

Education:
  • Undergraduate: Francis Marion College, BS, 1978
  • Postgraduate: University of South Carolina, PhD, 1985
  • Fellowship: Bowman Gray School of Medicine, 1985-88
Interests:
  • Teaching: Atherosclerosis and Arterial Connective Tissue Metabolism, Physiological and Pathological Calcification, Proteoglycan Biosysnthesis
  • Research: Cardiovascular Disease, Atherosclerosis Progression and Regression, Osteoporosis, Molecular Mechanisms of Regulation of Arterial and Bone Metabolism, Steroid Hormones and Hormone Receptors in Health and Disease, Molecular Genetics, Nutrition
Current Project(s): Sex Hormone Receptors and Regulation of Gene Expression Tissue Specificity of Traditional and Alternative Hormone Replacement Therapies

Sex hormones (estrogens, progestogens, and androgens) exert their effects on target tissues through specific hormone receptors. Alterations in the levels of these hormones through aging, menopause, or pharmacologic interventions have diverse effects on different target tissues, sometimes promoting health in one tissue and disease in another. Our previous work demonstrated that reproductive and non-reproductive tissues from non-human primates express both the classical ER (ERalpha) and a newly discovered estrogen receptor (ERbeta). Coronary arteries from females as well as males were found to express relatively high levels of ERbeta mRNA compared to ERalpha, suggesting this receptor could play a role in the protective effects of estrogens against atherosclerosis. ERbeta/ERalpha mRNA ratios were found to be highest in hippocampus and hypothalamus, intermediate in ovary, artery and uterus, and low in mammary and hepatic tissues. Since these receptors have unique properties, their absolute and relative expression may be important factors in tissue-specific responses to estrogen(s) and other hormones. Some phytoestrogens, for example, have a higher affinity for ERbeta.

My primary research interest relates to the effects of estrogen and estrogen-like compounds on gene expression in traditional and non-traditional target tissues and the role of the estrogen receptors, ERalpha and ERbeta. We have several projects under way: the first involves a set of archived non-human primate target tissues in which we are determining of the effects of estrogen(s) and other hormone replacement therapies on 1) expression of estrogen, androgen, and progesterone receptors and 2) global mRNA expression. This project will allow us to determine relationships between effects of various hormones, individual receptor levels, and gene expression in reproductive and non-reproductive target tissues. A second project is designed to determine the direct effects of estrogens on mRNA expression in human vascular smooth muscle and endothelial cells, and the relative importance of ERalpha vs. ERbeta in those effects. Both of the above studies are employing functional genomics and the emerging cDNA microarray technologies to explore hormone effects on global gene expression. A third project is designed to determine the role that androgens play in the effects of oral contraceptives on skeletal and reproductive tissues. Overall this work will provide valuable information regarding tissue-specific effects of hormone therapies and the importance of sex hormone receptor expression in site-specific responses to these therapies.

Recent Publications:

Shively CA, Wood CE, Register TC, Willard SL, Lees CJ, Chen H, Sitruk-Ware RL, Tsong YY, Cline JM. Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys. Psychoneuroendocrinology. 2007 Sep 1; [Epub ahead of print]

Lees CJ, Kaplan JR, Chen H, Jerome CP, Register TC, Franke AA. Bone mass and soy isoflavones in socially housed, premenopausal macaques. Am J Clin Nutr. 2007 Jul;86(1):245-50.

Walker SE, Adams MR, Franke AA, Register TC. Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys. Atherosclerosis. 2007 Mar 14; [Epub ahead of print]

Sastry KS, Karpova Y, Prokopovich S, Smith AJ, Essau B, Gersappe A, Carson JP, Weber MJ, Register TC, Chen YQ, Penn RB, Kulik G. Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J Biol Chem. 2007 May 11;282(19):14094-100.

Sikoski P, Register TC, Lees CJ, Lundeen S, Hutchison J, Brown KH, Cline JM.  Effects of two novel selective estrogen receptor modulators, raloxifene, tamoxifen, and ethinyl estradiol on the uterus, vagina and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis). Am J Obstet Gynecol. 2007 Jan;196(1):75.e1-7.

Wood CE, Sitruk-Ware RL, Tsong YY, Register TC, Lees CJ, Cline JM. Effects of estradiol with oral or intravaginal progesterone on risk markers for breast cancer in a postmenopausal monkey model. Menopause. 2007 Jul-Aug;14(4):639-47.

Lehtinen AB, Burdon KP, Lewis JP, Langefeld CD, Ziegler JT, Rich SS, Register TC, Carr JJ, Freedman BI, Bowden DW. Association of alpha2-Heremans-Schmid glycoprotein polymorphisms with subclinical atherosclerosis. J Clin Endocrinol Metab. 2007 Jan;92(1):345-52.

Wood CE, Register TC, Cline JM. Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys. Carcinogenesis. 2007 Apr;28(4):801-8.

Wood CE, Register TC, Lees CJ, Chen H, Kimrey S, Cline JM. Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys. Breast Cancer Res Treat. 2007 Jan;101(2):125-34.

Adams MR, Golden DL, Chen H, Register TC, Gugger ET. A diet rich in green and yellow vegetables inhibits atherosclerosis in mice. J Nutr. 2006 Jul;136(7):1886-9.

Register TC, Lenchik L, Hsu FC, Lohman KK, Freedman BI, Bowden DW, Carr JJ. Type 2 diabetes is not independently associated with spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Bone. 2006 Sep;39(3):628-33.

Stute P, Register TC, Blair RM, Cline JM. Effects of tibolone on estrogen biosynthesis in the mammary tissue of postmenopausal monkeys. Menopause. 2006 Mar-Apr;13(2):232-40.

Wood CE, Register TC, Franke AA, Anthony MS, Cline JM. Dietary soy isoflavones inhibit estrogen effects in the postmenopausal breast. Cancer Res. 2006 Jan 15;66(2):1241-9.

Adams MR, Golden DL, Williams JK, Franke AA, Register TC, Kaplan JR. Soy protein containing isoflavones reduces the size of atherosclerotic plaques without affecting coronary artery reactivity in adult male monkeys. J Nutr. 2005 Dec;135(12):2852-6.

Conner P, Register TC, Skoog L, Tani E, von Schoultz B, Cline JM. Expression of p53 and markers for apoptosis in breast tissue during long-term hormone therapy in cynomolgus monkeys. Am J Obstet Gynecol. 2005 Jul;193(1):58-63.

Hsu FC, Lenchik L, Nicklas BJ, Lohman K, Register TC, Mychaleckyj J, Langefeld CD, Freedman BI, Bowden DW, Carr JJ. Heritability of body composition measured by DXA in the diabetes heart study. Obes Res. 2005 Feb;13(2):312-9.

Shively CA, Register TC, Friedman DP, Morgan TM, Thompson J, Lanier T. Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis). Biol Psychol. 2005 Apr;69(1):67-84.

Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, Anthony MS, Blair RM, Wagner JD, Clarkson TB. Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys. J Clin Endocrinol Metab. 2005 Mar;90(3):1734-40.

Lenchik L, Hsu FC, Register TC, Lohman KK, Freedman BI, Langefeld CD, Bowden DW, Carr JJ. Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Calcif Tissue Int. 2004 Oct;75(4):305-12.

Register TC, Burdon KP, Lenchik L, Bowden DW, Hawkins GA, Nicklas BJ, Lohman K, Hsu FC, Langefeld CD, Carr JJ. Variability of serum soluble intercellular adhesion molecule-1 measurements attributable to a common polymorphism. Clin Chem. 2004 Nov;50(11):2185-7.

Shively CA, Register TC, Grant KA, Johnson JL, Cline JM. Effects of social status and moderate alcohol consumption on mammary gland and endometrium of surgically postmenopausal monkeys. Menopause. 2004 Jul-Aug;11(4):389-99.

Wood CE, Register TC, Anthony MS, Kock ND, Cline JM. Breast and uterine effects of soy isoflavones and conjugated equine estrogens in postmenopausal female monkeys. J Clin Endocrinol Metab. 2004 Jul;89(7):3462-8.

Wood CE, Cline JM, Anthony MS, Register TC, Kaplan JR. Adrenocortical effects of oral estrogens and soy isoflavones in female monkeys. J Clin Endocrinol Metab. 2004 May;89(5):2319-25.

Lenchik L, Register TC, Bowden DW. Response to letter to the editor. Bone. 2004 May;34(5):917.

Simon NG, Kaplan JR, Hu S, Register TC, Adams MR. Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones. Horm Behav. 2004 Apr;45(4):278-84.

Wood CE, Borgerink H, Register TC, Scott L, Cline JM. Cervical and vaginal epithelial neoplasms in cynomolgus monkeys. Vet Pathol. 2004 Mar;41(2):108-15.

Lenchik L, Shi R, Register TC, Beck SR, Langefeld CD, Carr JJ. Measurement of trabecular bone mineral density in the thoracic spine using cardiac gated quantitative computed tomography. J Comput Assist Tomogr. 2004 Jan-Feb; 28(1): 134-9.

Cline JM, Franke AA, Register TC, Golden DL, Adams MR. Effects of dietary isoflavone aglycones on the reproductive tract of male and female mice. Toxicol Pathol. 2004 Jan-Feb; 32(1): 91-9.

Ivester P, Shively CA, Register TC, Grant KA, Reboussin DM, Cunningham CC. The effects of moderate ethanol consumption on the liver of the monkey, Macaca fascicularis. Alcohol Clin Exp Res. 2003 Nov;27(11):1831-7.

Lenchik L, Register TC, Hsu FC, Lohman K, Nicklas BJ, Freedman BI, Langefeld CD, Carr JJ, Bowden DW. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone. 2003 Oct;33(4):646-51.

Register TC, Jayo MJ, Anthony MS. Soy phytoestrogens do not prevent bone loss in postmenopausal monkeys. J Clin Endocrinol Metab. 2003 Sep;88(9):4362-70.

Register TC, Cline JM, Shively CA. Health issues in postmenopausal women who drink. Alcohol Res Health. 2002; 26(4): 299-307.

Shively CA, Grant KA, Register TC. Effects of long-term moderate alcohol consumption on agonistic and affiliative behavior of socially housed female cynomolgus monkeys (Macaca fascicularis). Psychopharmacology (Berl). 2002 Dec;165(1):1-8.

Cline JM, Register TC, Clarkson TB. Effects of tibolone and hormone replacement therapy on the breast of cynomolgus monkeys. Menopause. 2002 Nov-Dec;9(6):422-9.

Register TC, Wagner JD, Zhang L, Hall J, Clarkson TB. Effects of tibolone and conventional hormone replacement therapies on arterial and hepatic cholesterol accumulation and on circulating endothelin-1, vascular cell adhesion molecule-1, and E-selectin in surgically menopausal monkeys. Menopause. 2002 Nov-Dec;9(6):411-21.

Adams MR, Golden DL, Register TC, Anthony MS, Hodgin JB, Maeda N, Williams JK. The atheroprotective effect of dietary soy isoflavones in apolipoprotein E-/- mice requires the presence of estrogen receptor-alpha. Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1859-64.

Lees CJ, Register TC, Turner CH, Wang T, Stancill M, Jerome CP. Effects of raloxifene on bone density, biomarkers, and histomorphometric and biomechanical measures in ovariectomized cynomolgus monkeys. Menopause. 2002 Sep-Oct;9(5):320-8.

Cline JM, Register TC, Clarkson TB. Comparative effects of tibolone and conjugated equine estrogens with and without medroxyprogesterone acetate on the reproductive tract of female cynomolgus monkeys. Menopause. 2002 Jul-Aug;9(4):242-52.

Vidal JD, Register TC, Gupta M, Cline JM. Estrogen replacement therapy induces telomerase RNA expression in the macaque endometrium. Fertil Steril. 2002 Mar;77(3):601-8.

Williams JK, Hall J, Anthony MS, Register TC, Reis SE, Clarkson TB. A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys. Menopause. 2002 Jan-Feb;9(1):41-51.

Adams MR, Golden DL, Anthony MS, Register TC, Williams JK. The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins. J Nutr. 2002 Jan;132(1):43-9.

Register TC, Carlson CS, Adams MR. Serum YKL-40 is associated with osteoarthritis and atherosclerosis in nonhuman primates. Clin Chem. 2001 Dec;47(12):2159-61.

Cline JM, Soderqvist G, Register TC, Williams JK, Adams MR, Von Schoultz B. Assessment of hormonally active agents in the reproductive tract of female nonhuman primates. Toxicol Pathol. 2001 Jan-Feb;29(1):84-90. Review