The short-term research objective, as outlined in the current proposal, is to elucidate the cellular mechanisms underlying the action(s) of individual modulators (ie, dopamine) of prolactin secretion. The long-term research objective is to establish a basis for understanding integrated neuroendocrine function during physiological changes in prolactin secretion. Incorporation of a perfusion technique to measure temporal patterns of prolactin secretion and an imaging technique to measure intracellular [Ca2+], will yield greater insights into mechanisms of stimulus-secretion coupling. Prolactin is a pituitary hormone involved in numerous reproductive and nonreproductive processes. Unlike most endocrine cells, which do not secrete unless stimulated, the pituitary lactotrope requires constant inhibition to keep its secretory activity under control. The primary physiological inhibitor of prolactin secretion is dopamine. However, dopamine is involved in a complex interplay with other neurotransmitters and hormones. The dynamics and complexity of this system have been the major impediments to our understanding of the control of prolactin. Consequently, it is necessary to define the mechanisms of action of each of these regulators before we can understand their integrated actions in vivo. Elucidation of these mechanisms will be achieved through the application of diverse experimental approaches (immunology, biochemistry, electrophysiology) in a concerted manner to functionally-defined prolactin-secreting cells. Measurements of the secretory and ionic activity in single lactotropes will provide insights into the basis of their functional heterogeneity, while measurement of prolactin release from populations of cohort cells will provide information on the integrated, temporal profile of their secretory behavior. Prolactin hypersecretion is the major neuroendocrine cause of infertility in women and importance in men. The defect in prolactin-secreting tumors appears to be an intrinsic abnormality of the lactotropes, leading to loss of dopaminergic inhibition. The research proposed herein will provide a framework in which to examine selected aspects of cell function and abnormalities associated with pathologies of prolactin secretion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK002019-03
Application #
3072618
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1991-01-15
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Ho, M Y; Kao, J P; Gregerson, K A (1996) Dopamine withdrawal elicits prolonged calcium rise to support prolactin rebound release. Endocrinology 137:3513-21
Gregerson, K A; Chuknyiska, R; Golesorkhi, N (1994) Stimulation of prolactin release by dopamine withdrawal: role of calcium influx. Am J Physiol 267:E789-94
Gregerson, K A; Golesorkhi, N; Chuknyiska, R (1994) Stimulation of prolactin release by dopamine withdrawal: role of membrane hyperpolarization. Am J Physiol 267:E781-8