Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6793648 | Hormones and Behavior | 2018 | 8 Pages |
Abstract
Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22â¯h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200â¯Î¼g/kg), a GPER-1 agonist (G-1; 0-1600â¯Î¼g/kg), and a GPER-1 antagonist (G-36; 0-80â¯Î¼g/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40â¯Î¼g/kg G-36 followed 30â¯min later by s.c. injections of vehicle or 200â¯Î¼g/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1â¯h of drug treatment, and feeding remained suppressed for 22â¯h following PPT treatment and 4â¯h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1â¯h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22â¯h. These findings demonstrate that selective activation of ERα produces a rapid (within 1â¯h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect.
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Authors
Michael J. Butler, Ryan P. Hildebrandt, Lisa A. Eckel,