Publications
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Peer Reviewed Publications
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Perrot-Sinal TS, Davis AM, Gregerson KA, Kao JPY, McCarthy MM. (/01/2001). Estradiol enhances increases in cytosolic calcium induced by excitatory GABA in neonatal hypothalamic neurons. Endocrinology, 142, 2238-2243.
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Gregerson KA, Flagg TP, Anderson M, Lauring O, Horel JS, ONeill TJ, Welling PA. (/01/2001). Identification of the G-protein-coupled, inward rectifying potassium channel gene products in rat anterior pituitary gland. Endocrinology, 142, 2820 - 2832.
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Positions and Work Experience
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1975
-1976
Laboratory technician
Department of Biology
Illinois Wesleyan University.
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1977
-1978
Teaching assistant
Department of Physiology and Biophysics University of Nebraska Medical Center, School of Medicine
Omaha, NE
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1978
-1980
Physiology teacher (Endocrinology, Reproductive Physiology, and G.I. sections)
University of Nebraska Medical Center, School of Nursing
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1977
-1981
Predoctoral Fellow
Department of Physiology and Biophysics, University of Nebraska Medical Center, School of Medicine
Omaha, NE.
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1982
-1985
Postdoctoral Fellow
Department of Physiology, University of Maryland, School of Medicine
Baltimore, MD
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1986
Postdoctoral Fellow
Department of Physiology, University of North Carolina at Chapel Hill, School of Medicine
Chapel Hill, NC
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1987
-1995
Assistant Professor
Departments of Pediatrics and Physiology, University of Maryland at Baltimore, School of Medicine
Baltimore, MD.
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1995
-1998
Associate Professor with tenure
Departments of Pediatrics and Physiology, University of Maryland at Baltimore, School of Medicine
Baltimore, MD.
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1998
-2001
Associate Professor with tenure
Department of Obstetrics/Gynecology and Reproductive Sciences and Department of Physiology, University of Maryland at Baltimore, School of Medicine
Baltimore, MD.
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2001
-2004
Associate Professor, Department of Pharmacological and Physiological Science
Saint Louis University, School of Medicine
St. Louis, MO.
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2004
to Present
Associate Professor
Division of Pharmaceutical Sciences, University of Cincinnati, College of Pharmacy
Cincinnati, OH.
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2004
to Present
Adjunct Faculty Member
Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine
St. Louis, MO.
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Education
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Institution:Illinois Wesleyan University
Bloomington, IL.
B.A.
1976
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Institution:University of Nebraska School of Medicine
Omaha, NE.
Ph.D.
1981
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Keywords
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Prolactin, Neuroendocrinology, Stimulus-Secretion Coupling, Stress, Reproduction, Electrophysiology
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Research and Practice Interests
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Laboratory of Karen A. Gregerson, Ph.D.
Neuroendocrinology and Hormone Signaling
The work in my laboratory has involved the study of the regulatory mechanisms underlying hormone actions. This work has focused on the regulation of prolactin (PRL), an anterior pituitary hormone with profound effects on female fertility. Normal PRL levels are required for female fertility, but excess secretion of PRL is the major neuroendocrine-related pathology associated with female infertility. To provide a rational framework for understanding the normal physiology of PRL secretion and for treating associated pathologies, it is essential to elucidate the cellular and molecular mechanisms of PRL regulation. Normally, PRL secretion is under tonic inhibition by hypothalamic dopamine (DA). Periodic, physiological surges of PRL in females require a withdrawal from this dopaminergic inhibition. Because of DA’s essential role, our attention has focused on the cellular and molecular basis of DA action on the lactotroph. This work has led us to identify a DA-activated potassium channel in normal lactotrophs that mediates DA’s regulation of membrane excitability and patterns of cytosolic [Ca2+] fluctuations in these cells. Using modern molecular techniques, we were able to clone this novel channel and have now also generated genetically modified mice in which the function of this signal transducer is either knock-out (“loss-of-function”) or enhanced (“gain-of function”). We are using these models to elucidate the role of this effector protein in generating physiological patterns of PRL secretion.
More recent projects in the lab have involved the generation of novel mouse strains that have been humanized with regard to the structural gene, tissue expression and secretory patterns of PRL. To create these strains, we have utilized the two distinct PRL promoters that are present in humans to drive pituitary-specific PRL expression (“endocrine” PRL) and extra-pituitary expression of PRL (“paracrine or autocrine” PRL). Extra-pituitary PRL expression in the uterus and mammary gland of humans has been proposed to play essential roles in implantation, decidualization and mammary gland development. However, this promoter is not found in rodents and PRL penetrance in these extrapituitary tissues is low, leaving an absence of a suitable experimental animal model for the study of extrapituitary PRL. We are crossing these new strains onto the mouse PRL knock-out background to produce models in which the endocrine actions of pituitary PRL and paracrine actions of extra-pituitary PRL can be studied in isolation. In addition, both pituitary and locally-produced PRL have been implicated in the progression and metastatic behavior of human breast cancer. Therefore, we chose to have these mice express human PRL with the ultimate goal of generating superior experimental hosts for xenograft studies with human cancer cells and human neoplastic cell lines.
Finally, our laboratory has an active collaboration with that of Dr. Nelson Horseman, also of the University of Cincinnati. Our collaborative work includes a project on the role of hormones in the adaptation of mice to combinations of trauma and despair-provoking stresses, so as to mimic the complex pattern of internal and external challenges that give rise to morbidity in traumatically injured humans. A second collaborative project is underway, examining hormonal and neurotransmitter changes during pregnancy and lactation that underlie alterations of mood in the peri- and post-partum periods.
Trainees participate in all aspects of this research, both technically and intellectually. They will use state-of-the-art techniques in patch clamping, fluorescence imaging and molecular biology. By making available such leading-edge methodology, doctoral and postdoctoral fellows entering this research program have the opportunity to become skilled in new approaches to research. Moreover, this multi-faceted study of the signal transduction mechanisms underlying prolactin regulation embodies an integrative approach to a scientific question. Such an integrative philosophy is critical in developing the reasoning and conceptualization processes required for developing successful careers of both basic scientists and clinical scientists.
Current lab members and their projects:
Heather Hale, Ph.D. student – human PRL transgenic mice project and signal transduction mechanisms of dopamine in pituitary lactotrophs
Nick Jury, Ph.D. student – interactions of peripheral and central 5HT systems during lactation and resulting alterations in mood
Cheryl Minges, M.S. student – mechanisms in estrogen regulation of pituitary PRL using mice with lactotroph-specific deletion of ERa
Donna Buckley, Principal Research Assistant -- molecular biology of lactotroph regulation
Michael Murawsky, Senior Research Assistant – membrane excitability and cytosolic [Ca2+] regulation in pituitary lactotrophs
Erin Pangallo, Research Assistant and Veterinary Technician – Everything!
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Courses Taught
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Instr. Method:lecture, student participation
Max Enroll:20
Actual Enroll:15
Level:Graduate
This course is an introductory graduate level course on Molecular and Cellular Neuroscience and is a core course for the Neuroscience Graduate Program.
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26-NS-840 SURVEY OF RESEARCH
Level:Graduate
This is a core course of the Neuroscience Graduate Program and serves as an introduction to current research in the neuroscience community at the University of Cincinnati.
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25-PHID-701 SEM PHARM SCIENCES
Instr. Method:research lectures and journal club
Level:Graduate
Weekly research seminars are given by outside investigators. Students prepare presentations/discussions of related scientific literature the week before.
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25-PHID-702 SEM PHARM SCIENCES
Instr. Method:student research presentations
Level:Graduate
M.S. and Ph.D. students in the College of Pharmacy present their research to students, faculty and staff.
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25-PHID-703 SEM PHARM SCIENCES
Instr. Method:student research presentations
Level:Graduate
M.S. and Ph.D. students in the College of Pharmacy present their research to students, faculty and staff.
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25-PBIO-613 ANATOMY AND PHYSIOL
Instr. Method:lecture, student paper
Max Enroll:96
Actual Enroll:96
Level:Graduate
This is a core course in the PharmD curriculum.
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26-MCP-952 MOLECULAR PHYS II
Instr. Method:literature presentation/discussion, lectures
Level:Graduate
This course covers receptor physiology and intracellular signaling pathways.
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Reproductive Pharmacology-Physiology
25-PBIO-750
Instr. Method:lecture, student participation
Level:Graduate
This is a graduate level course in Reproductive Physiology for PharmD, Ph.D., and M.S. students.
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