OHSU

M. Susan Smith

The hypothalamus is the primary area within the brain where neurons reside that regulate important functions, such as food intake, energy balance and reproduction. The hypothalamus also serves to integrate signals from peripheral tissues within the body, or from the external environment, that can alter these functions. 

 

The goal of the Smith laboratory is to elucidate the neuroendocrine control systems governing food intake, energy balance and reproductive function. These scientists are studying a number of different populations of hypothalamic neurons that control food intake and energy balance and receive signals from peripheral tissues that provide information about energy balance. In response to a negative energy balance signal, appetite and food intake are increased, whereas the rate of metabolism is decreased. The opposite occurs in response to positive energy balance. Having an understanding of the neural substances important in the regulation of food intake and energy balance will lead to better treatments for obesity, a condition that is reaching epidemic proportions in the United States.

 

It is particularly interesting that the functions of food intake and energy balance are highly integrated with that of reproduction. In times of prolonged negative energy balance, such as starvation, normal reproductive function stops. The same is true of conditions such as anorexia nervosa, bulimia, and exercise-induced amenorrhea. A major focus of the Smith lab is to characterize the neuroanatomical framework by which key hypothalamic appetite-regulating neuropeptide systems regulate gonadotropin releasing hormone neurons (GnRH, the hypothalamic neuropeptide that regulates reproduction), and on identifying signals that convey the status of energy balance to GnRH neurons.

 

The other area of focus is the role of the maternal environment in development of the offspring, specifically as it relates to the risk of obesity and diabetes. The nonhuman primate model of maternal obesity developed by the Grove/Smith labs has resulted in highly important findings relevant to human health. Eating a diet high in fat during pregnancy has long lasting effects on the offspring that likely increase its propensity to develop obesity, diabetes, and behavioral abnormalities. This NHP model is being used to examine possible therapeutic interventions during pregnancy that can prevent or reduce the risks of these developmental abnormalities.

 

A number of complementary techniques are being used for these studies: immunocytochemistry to identify neuronal phenotypes, in situ hybridization and RT-PCR to quantify mRNA levels, retrograde and anterograde tracers to determine neuronal projections contacted by the cells, confocal microscopy to analyze neuroanatomical data, electrophysiology to study direct effects of neuropeptides on specific hypothalamic neurons, and DNA microarray technology to identify novel hypothalamic genes.


BIOGRAPHY

 

M. Susan Smith served as Director of the Oregon National Primate Research Center from 1994-2007 and is currently a Senior Scientist in the Division of Diabetes, Obesity, & Metabolism and in the Division of Neuroscience, and a professor of physiology and pharmacology in the OHSU School of Medicine. After receiving an M.S. from Florida State University and a Ph.D. from the University of Georgia in 1972, Smith did a postdoctoral fellowship in physiology at Emory University. She was a faculty member in the Department of Physiology at the University of Massachusetts Medical School and in the Department of Physiology at the University of Pittsburgh where she was promoted to professor. She has served on the editorial boards of Biology of Reproduction, Current Opinion in Endocrinology & Diabetes, Endocrinology, Frontiers in Neuroendocrinology, and Neuroendocrinology.  She has served on a number of NIH committees, including the Biochemical Endocrinology Study Section, the NICHD Population Research Committee the NICHD Special Emphasis Panel, and the NICHD Pediatrics Study Section. Dr. Smith has held a number of leadership positions in professional societies, including serving as President of The Endocrine Society. She currently serves on the OHSU Foundation Board of Trustees and chairs the Medical Research Foundation of Oregon Research and Education Committee.

 

KEY PUBLICATIONS


Smith MS, True C, Grove KL. The neuroendocrine basis of lactation-induced suppression of GnRH: role of kisspeptin and leptin. Brain Research 1364:139-152, PMCID: PMC3118984, 2010.

 

True C, Kirigiti M, Ciofi P, Grove KL, Smith MS.  Characterization of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. J Neuroendocrinol 23:52-64, PMCID: PMC3118985, 2010.   

 

True C, Kirigiti MA, Kievit P, Grove KL, Smith MS. Leptin is not the critical signal for kisspeptin or luteinising hormone restoration during the exit from negative energy balance. J Neuroendocrinol 23: 1099-112, PMID: 21518032, 2011. 

 

True C, Grove KL, Smith MS. Beyond leptin: emerging candidates for the integration of metabolic and reproductive function during negative energy balance. Front Endocrinol 2:53 (1-12), PMCID: PMC3355832, 2011.

 

Sullivan E, Smith MS, Grove KL. Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinol 93: 1-8, PMID: 21079387, 2011. 

 

Lee SJ, Kirigiti M, Lindsley SR, Loche A, Madden CJ, Morrison SF, Smith MS, Grove KL.  Efferent projections of neuropeptide Y-expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models. J Comp Neurol 521: 1891-1914, PMCID: PMC3618613, 2013.

 

See a full listing of Dr. Smith's publications.