Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats

Horm Behav. 2018 Jul;103:54-61. doi: 10.1016/j.yhbeh.2018.05.018. Epub 2018 Jun 7.

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 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/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 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 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 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 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.

Keywords: Estrogen; Food intake; G-1; PPT; Rapid effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclopentanes / pharmacology
  • Eating / drug effects*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / agonists*
  • Estrogens / pharmacology*
  • Female
  • Ovariectomy
  • Phenols / pharmacology
  • Pyrazoles / pharmacology
  • Quinolines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptors, G-Protein-Coupled / agonists*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Cyclopentanes
  • Estrogen Receptor alpha
  • Estrogens
  • Gper1 protein, rat
  • Phenols
  • Pyrazoles
  • Quinolines
  • Receptors, G-Protein-Coupled
  • Selective Estrogen Receptor Modulators
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
  • Estradiol