Estrogen regulation of angiotensin II-induced water intake in the female rat / Lori Rogers Kisley.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Kisley, Lori Rogers.

Contributor:

Fluharty, Steven J., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Neurosciences.

Academic Dissertations as Topic.

Medical Subjects:

Neurosciences.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Physical Description:

xv, 176 pages : illustrations ; 29 cm

Production:

1999.

Summary:

Angiotensin II (AngII), a peptide hormone essential for cardiovascular and body fluid homeostasis, stimulates a well-characterized thirst response in the rat and is an excellent model system in which to study water intake behavior. AngII-induced thirst is influenced by the female rat estrous cycle, although the mechanism underlying this regulation is not well understood. The current experiments demonstrate that estrogen regulates AngII-induced thirst in female rats when given in doses and a time course that mimics the normal endocrine profile of the estrous cycle. It was also revealed that the effects are dose dependent and blockable with the anti-estrogen, CI-628. A modulatory role for progesterone was not observed in this system.

This project also revealed potential mechanisms by which estrogen regulates AngII-induced water intake. Quantitative autoradiography was utilized to determine the brain region and AngII receptor subtype influenced by estrogen treatment. Estrogen decreased AT1 receptor binding in the subfornical organ (SFO), a forebrain circumventricular organ necessary for AngII-induced thirst. We also used mRNA expression profiling to compare forebrain mRNA from vehicle- and estrogen-treated female rats. This study revealed a decrease in AT1 receptor mRNA levels following estrogen treatment. Thus, estrogen may act directly on the SFO to regulate AT1 expression. This decrease in AngII responsivity may explain the estrogen attenuation of AngII-induced thirst.

Finally, experiments were undertaken to determine the effects of estrogen on neuronal activity using c-Fos immunohistochemistry. AngII induced c-Fos expression in forebrain nuclei involved in fluid balance, specifically the OVLT, median preoptic nucleus, SFO, supraoptic nucleus and paraventricular nucleus (PVN). Estrogen increased AngII-induced c-Fos expression in the lateral magnocellular neurons of the PVN, which project to the posterior pituitary and release vasopressin or oxytocin into the circulation. As both hormones influence fluid balance, estrogen modulation may serve to maintain fluid levels when intake behavior is attenuated. Taken together, these experiments suggest that estrogen regulates water intake and fluid balance through interactions with multiple peptidergic systems in the brain.

Notes:

Adviser: Steven J. Fluharty.

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 1999.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 99-37742.

OCLC:

187475710