OHSU

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 appetide-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.

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.

Susan Smith, former director of the center, is a scientist 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 joined the Department of Physiology at the University of Massachusetts Medical School, where she was promoted to associate professor in 1979. In 1980 she moved to the Department of Physiology at the University of Pittsburgh and was promoted to professor. Smith accepted the directorship of the Primate Center in 1994.

KEY PUBLICATIONS

Xu J, Han VZ, Kirigiti MA, Cowley MA, Grove KL, and Smith MS.  (2009) Suppression of basal spontaneous GnRH neuronal activity during lactation:  Role of inhibitory effects of neuropeptide Y.  Endocrinology 150:333-340. PMID:18719019.

Xu J, Kirigiti MA, Grove KL, and Smith MS.  (2009) Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation: role of insulin and leptin. Endocrinology 150:4231-4240. PMID:19470705.