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Assistant Professor |
Training
B.A., Biology, 1997, Williams College
Appointments
Postdoctoral Fellow, Department of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, 2003-2005.
Postdoctoral Trainee, Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 2006-2007.
Instructor, Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 2007-2009.
Research Interests
My laboratory’s interests lie in understanding hypothalamic homeostatic mechanisms controlling body weight and fertility and the interactions between these two systems. The brain blocks reproduction in animals under metabolic stress. Within the hypothalamus, energy deficits suppress gonadotropin-releasing hormone (GnRH) release from a sub-population of neurons that maintain fertility. Anorexia, cachexia, and excessive exercise suppress reproductive cyclicity in humans and with it the estrogen release essential for bone health. Fully 5% of women of reproductive age suffer from infertility related to eating disorders. Furthermore, the incidence of exercise-related anovulation may reach as high as 61% in gymnasts and 78% in runners. On the opposite end of the spectrum, obesity and diabetes also negatively affect fertility. As rates of these diseases rise, it is urgent that we unravel the hypothalamic homeostatic mechanisms controlling body weight and fertility and the interactions between these two systems.
The hypothesis underlying my research is that circulating metabolic factors (such as leptin, insulin, ghrelin, glucose, LC-FAs or PYY3-36) are perceived directly or indirectly by GnRH neurons of the hypothalamus and convey information that prevents GnRH release during a state of negative energy balance. Determining the mechanisms behind this metabolic-reproductive connection will provide much needed targets for medical treatment. The cornerstone of my laboratory’s efforts is timed, targeted genetic manipulation using the power of tissue-specific gene deletion. Combined with anatomical, electrophysiological, and physiological techniques this approach offers a powerful tool for investigating the hypothalamic control of metabolism and fertility.
Publications
Fukuda M, Jones JE, Olson D, Hill J, Lee CE, Gautron L, Choi M, Zigman JM, Lowell BB, Elmquist JK. Monitoring FoxO1 localization in chemically identified neurons. J Neurosci. 2008 Dec 10; 28(50):13640-8. PMID: 19074037
Hill JW, Elmquist JK, Elias CF. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 2008 May; 294(5):E827-32. Epub 2008 Feb 19.
Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, Cowley MA, Cantley LC, Lowell BB, Elmquist JK. Acute effects of leptin require PI3K signaling in hypothalamic proopiomeanocortin neurons in mice. J Clin Invest. 2008 May 1; 118(5):1796-1805.
Hill JW. Leptin, Insulin, AND PTEN: Divergent effects on hypothalamic neurons explained? Cellscience Reviews. 2006; 3(2) 42-51.
Hill JW, Urban JH, Xu M, Levine JE. Estrogen Induces Neuropeptide Y (NPY) Y1 Receptor Gene Expression and Responsiveness to NPY in Gonadotrope-Enriched Pituitary Cell Cultures. Endocrinology. 2004 May; 145(5):2283-90.
Williams H, Connor DM, Hill JW. Testosterone decreases the potential for song plasticity in adult male zebra finches. Horm Behav. 2003 Dec; 44(5):402-12.
Hill JW, Levine JE. Abnormal response of the neuropeptide Y-deficient mouse reproductive axis to food deprivation but not lactation. Endocrinology. 2003 144(5):1780-6.
Hill JW, Xu M, Levine JE. Revisiting the reproductive functions of neuropeptide Y. Current Opinion in Endocrinology, Diabetes, and Obesity. 2002 9:203-214.
Xu M, Hill JW, Levine JE. Attenuation of luteinizing hormone surges in neuropeptide Y knockout mice. Neuroendocrinology. 2000 Nov; 72(5): 263-71
Xu M, Urban JH, Hill JW, Levine JE. Regulation of hypothalamic neuropeptide Y Y1 receptor gene expression during the estrous cycle: role of progesterone receptors. Endocrinology. 2000 Sep; 141(9): 3319-27