Lloyd M. Beidler Professor of Biology & Neuroscience
Reproductive neuroendocrinology; neural control of the pituitary gland.
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.
Selected Recent Publications
Poletini MO, McKee DT, Szawka RE, Bertram R, Helena CV, Freeman ME. Cervical stimulation activates A1 and locus coeruleus neurons that project to the paraventricular nucleus of hypothalamus. Brain Research Bulletin. 88:566-573. (2012)
Helena CV, Cristancho-Gordo R, Gonzalez-Iglesias AE, Tabak J, Bertram R, Freeman ME. Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol. 301(3):R676-R681. (2011)
Sirzen-Zelenskaya A, Gonzalez-Iglesias AE, de Monvel JB, Bertram R, Freeman ME, Gerber U, Egli M. Prolactin induces a hyperpolarizing current in rat paraventricular oxytocinergic neurons. J Neuroendocrinol. (2011) [in press]
Bertram R, Helena CV, Gonzalez-Iglesias AE, Tabak J, Freeman ME. A tale of two rhythms: The emerging roles of oxytocin in rhythmic prolactin release. J Neuroendocrinol. 22:778-784. (2010)
Poletini MO, Kennett JE, McKee DT, and Freeman ME. Central clock regulates the cervically-stimulated prolactin surges by modulation of dopamine and vasoactive intestinal polypeptide release in ovariectomized rat. Neuroendocrinology. 91:179-188. (2010)
Tabak J, Gonzalez-Iglesias AE, Toporikova N, Bertram R and Freeman ME. Variations in the response of pituitary lactotrophs to oxytocin during the rat estrous cycle. Endocrinology. 151:1806-1813. (2010)
Helena CV, McKee DT, Bertram R, Walker AM, Freeman ME. The rhythmic secretion of mating-induced prolactin secretion is controlled by prolactin acting centrally. Endocrinology. 150(7):3245-51. (2009)
Kennett JE, Poletini MO, Fitch CA, Freeman ME. Antagonism of oxytocin prevents suckling- and estradiol-induced, but not progesterone-induced, secretion of prolactin. Endocrinology. 150:2292-2299. (2009)
Oláh M, Fehér P, Ihm Z , Bácskay I, KissT, Freeman ME, Nagy G and Miklós Vecsernyés. Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes. Neuroendocrinology. 90:391-401. (2009)
Kennett JE, Poletini MO and Freeman ME. Vasoactive intestinal polypeptide modulates the estradiol-induced prolactin surge by entraining oxytocin neuronal activity. Brain Research. 1196:65 –73. (2008)
Poletini MO, McKee DT, Kennett JE, Doster J and Freeman ME. 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)
Sellix MT, Egli M, Poletini MO, McKee DT, Bosworth MD, Fitch CA and Freeman ME. 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)
Fowler CD, Freeman ME
, and Wang ZX. Newly proliferated cells in the adult male amygdala are affected by gonadal steroid hormones
. J Neurobiol
. 57:257-269. (2003) PDF
Freeman ME, Kanyicska B, Lerant A and Nagy G. Prolactin: structure, function and regulation of secretion. Physiological Reviews. 80:1523-1631. (2000)