Dr. Marc Freeman

Lloyd M. Beidler Professor of Biology & Neuroscience

Research Interest

Reproductive neuroendocrinology; neural control of the pituitary gland.

Current Projects

We study the way an important area of the brain, the hypothalamus, regulates the secretion of hormones from the pituitary gland that are involved in reproductive processes.

We are particularly interested in the control of secretion of prolactin, the hormone that controls milk synthesis in the mammary gland. The hypothalamus controls prolactin secretion from the anterior pituitary gland in an inhibitory manner. The inhibitory chemical made by nerve cells in the hypothalamus is dopamine. When released into the small blood supply connecting the hypothalamus with the pituitary gland, dopamine inhibits prolactin secretion. Prolactin-releasing stimuli, such as nursing by the hungry infant, inhibit dopamine release from the hypothalamus.

Using approaches such as culture of pituitary cells, radioimmunoassay for measuring prolactin, immunocytochemistry for visualizing dopamine nerve cells and their gene activity and high performance liquid chromatography along with electrochemical detection for measuring changes in dopamine in the brain we are pursuing the following problems:

It was previously believed that only one population of dopamine nerve cells in the hypothalamus affect prolactin secretion. We have identified 2 others which directly affect prolactin secretion and are in the process of characterizing the relative contribution of each
Prolactin inhibits its own secretion by activating dopamine nerve cells in the hypothalamus. We have identified prolactin receptors on dopamine nerve cells and are in the process of determining how prolactin regulates the activity of these cells.
We have found that dopamine is not only inhibitory to prolactin secretion, but under certain circumstances it can be stimulatory. We are in the process of determining how dopamine can both stimulate and inhibit the same pituitary cell that secretes prolactin.
We have discovered that a chemical found in the cells lining the blood vessels of all mammals, endothelin, affects the secretion of most of the anterior pituitary hormones. We are now determining the role endothelin plays in the secretion of each.

Pursuit of these problems have invariably led to many new, unanticipated, exciting questions that assume a place on our laboratory menu.

Publications

Selected Publications

Freeman, M.E., B. Kanyicska, A. Lerant and G. Nagy. Prolactin: structure, function and regulation of secretion. Physiological Reviews 80:1523-1631, 2000
Sellix, M.T. and M. E. Freeman. Circadian rhythms of neuroendocrine dopaminergic neurons neuronal activity in ovariectomized rats. Neuroendocrinology 77:59-70, 2003.
Kanyicska, B., M.T. Sellix and M. E. Freeman. Autocrine regulation of prolactin secretion by endothelins throughout the estrous cycle. Endocrine 20:53-58, 2003.
FOWLER C.D., M.E. FREEMAN AND WANG Z.X. NEWLY PROLIFERATED CELLS IN THE ADULT AMYGDALA ARE AFFECTED BY GONADAL STEROID HORMONES. J. NEUROBIOL 57:257-269, 2003.
Sellix, M.T., .M. Egli, R. P. Henderson and M. E. Freeman. Ovarian steroid hormones modulate circadian rhythms of neuroendocrine dopaminergic neuronal activity. Brain Research 1005:168-185, 2004.
Egli, M., R. Bertram, M.T. Sellix, and M. E. Freeman. Rhythmic secretion of prolactin in rats:Action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin. Endocrinology 145:3386-3394, 2004.
Stowe, J. R. Y. Liu, J. T. Curtis, M. E. Freeman and Z. Wang. Species differences in anxiety-related responses in male prairie and meadow voles: The effects of social isolation. Physiology and Behavior 86: 369-378, 2005.
Egli , M., Bertram, R., Toporikova, N., Sellix , M. T., Blanco, W. and M. E. Freeman. Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin. American Journal of Physiology: Endocrinology and Metabolism. 290: E566-E572, 2006.
Bertram, R., Egli, M. ,Toporikova, N. and M. E. Freeman. A mathematical model for the mating-induced prolactin rhythm of female rats. American Journal of Physiology: Endocrinology and Metabolism. 290: E573-E582, 2006.
Sellix, M. T., Egli, M.,. Poletini, M. O., . McKee, D. T., Bosworth, M.D., Fitch, C. A.and M.E. Freeman. Anatomical and functional characterization of circadian clock gene expression in neuroendocrine dopaminergic neurons. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 290: R1309-R1323, 2006.
Bertram, R., Tabak, J., Toporikova, N. and M. E. Freeman. Endothelin action on pituitary lactotrophs: one receptor, many GTP-binding proteins. Science STKE, 2006, Issue 319, pp. pe4, 24 January 2006, [DOI: 10.1126/stke.3192006pe4].
Freeman, M.E. The neuroendocrine control of the ovarian cycle of the rat. In: Knobil and Neill's Physiology of Reproduction. edited by Jimmy D. Neill, Academic Press, Third Edition, Vol 2, pp 2327-2388,2006.
Tabak, J., N. Toporikova, M. E. Freeman and R. Bertram. Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents. Journal of Computational Neuroscience 22: 211-222 , 2007.
McKee, D. T., M.O. Poletini, R. Bertram and M. E. Freeman. Oxytocin action at the lactotroph is required for prolactin surges in cervically stimulated ovariectomized rats. Endocrinology 148: 4649-4657, 2007.
Poletini, M. O., D. McKee, J.E. Kennett, J. Doster and M. E. Freeman. Knockdown of clock genes in the suprachiasmatic nucleus blocks the estradiol-induced prolactin surge and alters the circadian rhythm in the locus coeruleus of ovariectomized rats. American Journal of Physiology: Endocrinology and Metabolism. 293: E1325-E1334, 2007.
Toporikova N., J.Tabak, M. E. Freeman and R. Bertram. A-type K+ current can act as a trigger for bursting in the absence of a slow variable. Neural Computation; 20: 436-451, 2008
Kennett, J.E., M.O. Poletini and M.E. Freeman. Vasoactive intestinal polypeptide modulates the estradiol-induced prolactin surge by entraining oxytocin neuronal activity. Brain Research 1196:65 –73, 2008.
Freeman, M.E., D.T. McKee, M. Egli and R. Bertram. Biological and mathematical modeling approaches to defining the role of oxytocin and dopamine in the control of mating-induced PRL secretion. In: Neurobiology of the Parental Brain. Edited by Robert S. Bridges, Academic Press, pp 235- 247, 2008.