The estrogenic reduction in water intake stimulated by dehydration involves estrogen receptor alpha and a potential role for GLP-1

Abstract

It is well documented that estrogens inhibit fluid intake. Most of this research, however, has focused on fluid intake in response to dipsogenic hormone and/or drug treatments in euhydrated rats. Additional research is needed to fully characterize the fluid intake effects of estradiol in response to true hypovolemia. As such, the goals of this series of experiments were to provide a detailed analysis of water intake in response to water deprivation in ovariectomized female rats treated with estradiol. In addition, these experiments also tested if activation of estrogen receptor alpha is sufficient to reduce water intake stimulated by water deprivation and tested for a role of glucagon like peptide-1 in the estrogenic control of water intake. As expected, estradiol reduced water intake in response to 24 and 48 h of water deprivation. The reduction in water intake was associated with a reduction in drinking burst number, with no change in drinking burst size. Pharmacological activation of estrogen receptor alpha reduced intake. Finally, estradiol-treatment caused a leftward shift in the behavioral dose response curve of exendin-4, the glucagon like peptide-1 agonist. While the highest dose of exendin-4 reduced 10 min intake in both oil and estradiol-treated rats, the intermediate dose only reduced intake in rats treated with estradiol. Together, this series of experiments extends previous research by providing a more thorough behavioral analysis of the anti-dipsogenic effect of estradiol in dehydrated rats, in addition to identifying the glucagon like peptide-1 system as a potential bioregulator involved in the underlying mechanisms by which estradiol reduces water intake in the female rat.

Keywords: Drinking microstructure; Estradiol; Fluid intake; Satiation.

Figure 1.

EB treatment reduced water intake stimulated by 24 h water deprivation. (A) Analysis of licks in 10 min bins revealed that intake lasted for 40 minutes post water bottle access. Intake during the first 10 min was significantly greater than intake at all other timepoints. During this time, EB-treated rats had less licks than oil-treated rats and (B) a 1 min bin size analysis did not reveal any additional time specific changes in intake. (C) 40 min water intake was reduced when rats were treated with EB. (D) Licks for water were greatest during the first 10 min (bin 1) of testing. Regardless of time, EB treatment reduced licks, compared to Oil treatment. (E) EB treatment significantly reduced burst number, (F) but had no effect on burst size (licks/burst). ^#Less than oil during bin 1. ^aGreater than all other time bins. ^bLess than bin 1, but greater than bins 5-12. ^cLess than bin 1, but greater than bins 9-12. ^dLess than bins 1-3. ^eLess than bins 1-4. *Less than oil, p < 0.01. +Greater than licks during bins 2-4.

Figure 2.

Activation of ERα reduced water intake stimulated by 24 h water deprivation. (A) There was no significant difference in 40 min water intake between control and PPT treatment. (B) Licks for water were greatest during the first 10 min (bin 1) of testing. During this time, PPT treatment significantly reduced licks, compared to DMSO treatment. (C) PPT treatment had no effect on burst number, (D) nor reduced burst size (licks/burst). +Greater than licks during bins 2-4. ^#Less than 10 min oil group, p < 0.01.

Figure 3.

EB treatment reduced water intake stimulated by 48 h water deprivation. (A) 40 min water intake was reduced when rats were treated with EB. (B) Licks for water were greatest during the first 10 min (bin 1) of testing. EB treatment reduced licks, compared to Oil treatment, specifically within the first 10 min (bin 1) of testing (C) EB treatment significantly reduced burst number, (D) but had no effect on burst size (licks/burst). *Less than oil, p < 0.01. +Greater than licks during bins 2-4. ^#Less than 10 min oil group, p < 0.01.

Figure 4.

EB treatment produced a leftward shift in the dose response curve to exendin-4. (A) 40 min water intake was reduced by EB treatment. Water intake was reduced by treatment with 1.0 but not 0.1 μg/kg exendin-4 and intakes were further reduced by treatment with 3.0 μg/kg exendin-4. (B) Licks for water during the first 10 minutes were reduced by EB treatment. While the 1.0 μg/kg failed to reduce water intake in oil treated rats, there was a significant reduction in water intake when rats were treated with EB. The 3.0 μg/kg reduced licks in both oil and EB-treated rats. (C) 1.0 and 3.0 μg/kg exendin-4 significantly reduced burst number but (D) had no effect on burst size (licks/burst). *Less than oil, p < 0.01. #Less than 0 and 0.1 μg/kg exendin-4, p < 0.001. ^Less than 0, 0.1, and 1.0 μg/kg exendin-4, p < 0.001. +Less than vehicle treated rats, p < 0.05.