The Central Hypothesis of this renewal application is that under physiological conditions, prolactin (PRL) secretion is inhibited by dopamine (DA) and stimulated by oxytocin (OT) and that the activities of these neurons are regulated by higher hypothalamic input and PRL itself. We will test this hypothesis with a novel interdisciplinary experimental and mathematical approach to the following specific aims: (1) To determine the basis for a physiological interaction between DA, OT and PRL secretion, (2) To determine the physiological basis for the estrous cycle stage differences in the response of lactotropes to the PRL-releasing properties of OT, (3) To characterize the mechanism of action of OT on pituitary lactotropes and (4) To characterize the relationship of DA and other modulators of PRL release on OT-induced responses in lactotropes.
These aims are significant because they will challenge accepted dogma that PRL secretion in physiological circumstances is only under inhibitory control of hypothalamic DA.

Public Health Relevance

Current clinical approaches to manipulating prolactin secretion involve manipulation of dopamine. For example, the benign hypersecreting pituitary tumor known as a prolactinoma is treated with the dopamine agonists bromocryptine or cabergoline. Each of these drugs has side effects which have serious implications for patients'welfare. Indeed, as our preliminary data suggest, if prolactin secretion is also under the control of peptidergic releasing factors such as oxytocin, then this may be another approach to treating disorders of prolactin secretion. Moreover, prolactin has been implicated in disorders related to more than 300 of its other biological actions. Results from these studies may serve as an approach to treating these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043200-19
Application #
8211754
Study Section
Special Emphasis Panel (ZRG1-EMNR-E (02))
Program Officer
Malozowski, Saul N
Project Start
1992-05-01
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
19
Fiscal Year
2012
Total Cost
$431,148
Indirect Cost
$137,850
Name
Florida State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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