Professor, Neurology, Pathology
Professor, Cell Biology & Anatomy
Professor, Evelyn F. McKnight Brain Institute
Associate Department Head, Pathology
- University of Maryland, College Park, 1973 (B.S., Psychology)
- University of Maryland, Baltimore, 1981 (Ph.D., Physiology)
- University of Maryland, Baltimore, 1983 (M.D., Medicine)
- Phi Beta Kappa, 1973
- Rudolph Virchow Prize for Research in Pathology, University of Maryland, 1983
- John Davis Outstanding Residency Teaching Award, Dept. of Pathology, University of Arizona, 1995
- Basic Science Educator of the Year, University of Arizona College of Medicine, 1999
- Basic Science Educator of the Year, University of Arizona College of Medicine, 2000
- Basic Science Educator of the Year, University of Arizona College of Medicine, 2001
- Basic Science Educator of the Year Lifetime Award, University of Arizona College of Medicine, 2002
- Vernon and Virginia Furrow Award for Excellence in Innovation in Teaching, University of Arizona College of Medicine, 2007
The focus of my laboratory is the study of hormonal regulation of neuronal morphology and gene expression in the human brain. Specifically, we are examining changes that occur in the hypothalami in postmenopausal women. Menopause is characterized by a complete loss of ovarian estrogen secretion and a secondary rise in plasma levels of luteinizing hormone. We have observed an associated hypertrophy of neurons in the hypothalamic control region for reproduction. Our working hypothesis is that postmenopausal neuronal hypertrophy is secondary to the loss of the inhibitory feedback of ovarian steroids and is not simply a non-specific effect due to aging per se. Our finding of estrogen receptor mRNA in the hypertrophied nuerons is strong support for this hypothesis. We have also used in situ hybridization and computer microscopy to demonstrate that the enlarged neurons contain neurokinin B and substance P gene transcripts. Remarkably, the expression of these genes is markedly increased in the hypothalami of postmenopausal women. More recently, we have found that the increase in gene expression in postmenopausal women is duplicated by removal of the ovaries of rats. These studies provide evidence that the changes we have observed in postmenopausal women are due to ovarian withdrawal and not simply a nonspecific effect of aging. What is the function of the hypertrophied nuerons? We think they might be participating in the hypothalamic circuitry medicating estrogen negative feedback on gonadotropin secretion.
Menopause occurs within such a well-defined system and has consistent and dramatic changes in plasma hormones, endocrine organs and a readily identified loss of function. Therefore, we have the rare opportunity of studying human brains to answer basic biological questions.
Burke MC, Letts PA, Krajewski SJ and Rance, NE. Coexpression of dynorphin and neurokinin B immunoreactivity in the rat hypothalamus: Morphologic evidence of interrelated function within the arcuate nucleus, J. Comp. Neurol., 498, 712-726, 2006.
Bousfield GR, Butnev VY, Walton WJ, Nguyen VT, Huneidi J, Singh V, Kolli VS, Harvey DJ, Rance NE All-or-none N-glycosylation in primate follicle-stimulating hormone beta-subunits Mol. Cell. Endocrinol., 260-262:40-48, 2006.
Rometo, AM, Sally J. Krajewski, S.J., Voytko, M.L., Rance, N.E. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J. Clin. Endo. Metab., 92:2744-2750, 2007.
Michelle Burke (MSRP 2004, 2006): "Arcuate Neurokinin B Projections within the Rat Hypothalamus (2004)";" Characterizations of the Effects of a Molecular Neurotoxin on NK3 Receptor Expressing Neurons in the Median Preoptic Nucleus of the Rat (2006)."