Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.
Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.
Thammacharoen
Sumpun
S
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland.
Geary
Nori
N
Physiology and Behavior Group, Institute for Animal Sciences, ETH Zurich, CH-8603 Schwerzenbach, Switzerland; Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Lutz
Thomas A
TA
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, Switzerland.
Ogawa
Sonoko
S
Kansei, Behavior and Brain Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Asarian
Lori
L
Physiology and Behavior Group, Institute for Animal Sciences, ETH Zurich, CH-8603 Schwerzenbach, Switzerland. Electronic address: lasarian@ethz.ch.
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010636:Phenols; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D047628:Estrogen Receptor alpha; D004967:Estrogens; D010636:Phenols; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074283:estradiol 3-benzoate; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone