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Date Available
7-23-2028
Year of Publication
2026
Document Type
Master's Thesis
Degree Name
Master of Science (MS)
College
Arts and Sciences
Department/School/Program
Biology
Faculty
Jessica Santollo
Faculty
Jakub Famulski
Abstract
Estradiol (E2) inhibits water intake, but the mechanisms underlying this effect remain unclear. Glucagon-like peptide-1 (GLP-1) also suppresses fluid intake, and accumulating evidence suggests that estradiol enhances behavioral sensitivity to GLP-1 receptor activation. Therefore, this thesis examined whether estradiol enhances the anti-dipsogenic effects of GLP-1 receptor activation and whether endogenous GLP-1 signaling contributes to estradiol-induced suppression of drinking behavior. Ovariectomized (OVX) female rats were treated with estradiol benzoate (EB) or vehicle and tested in both angiotensin II-induced (AngII) and water deprivation-induced drinking paradigms. The effects of the GLP-1 receptor agonist exendin-4 and antagonist exendin-9 on water intake and drinking microstructure were assessed. Exendin-4 reduced water intake, and estradiol enhanced sensitivity to its fluid-suppressive effects, resulting in greater and more prolonged suppression of drinking behavior. In contrast, although exendin-9 increased drinking behavior, blockade of endogenous GLP-1 receptors did not abolish or attenuate the anti-dipsogenic effects of estradiol in either drinking model. Drinking microstructure analyses further indicated that estradiol and GLP-1 receptor activation influenced distinct components of drinking behavior, with estradiol primarily affecting measures associated with satiation and GLP-1 receptor activation influencing measures linked to the orosensory control of drinking. Together, these findings demonstrate that estradiol enhances responsiveness to GLP-1 receptor activation but does not require endogenous GLP-1 signaling to suppress water intake. These results provide new insights into the interaction between ovarian hormones and GLP-1 signaling in regulating fluid balance and may have important clinical implications for understanding sex differences in responses to GLP-1 receptor agonists pharmacotherapies.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2026.358
Archival?
Archival
Recommended Citation
Young, Grace Trinity, "ESTROGEN AND GLP-1 RECEPTOR SIGNALING IN THE REGULATION OF DRINKING BEHAVIOR IN FEMALE RATS" (2026). Theses and Dissertations--Biology. 119.
https://uknowledge.uky.edu/biology_etds/119
