Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats.
Part of the mechanism through which estradiol, acting via estrogen receptor (ERalpha) signaling, inhibits feeding in rats and mice is increasing the satiating potency of cholecystokinin (CCK) acting on peripheral CCK-1 receptors. Ingested lipid is a principal secretagogue of intestinal CCK, and intraduodenal lipid infusions elicit CCK-mediated satiation in animals and humans. Here we tested whether estradiol affects the satiating potency of intraduodenal lipid infusions in ovariectomized rats and, using c-Fos immunocytochemistry, searched for potential brain sites of ERalpha involved. Food-deprived ovariectomized rats with open gastric cannulas sham fed 0.8 m sucrose 2 d after estradiol (estradiol benzoate, 10 mug, sc) or vehicle injection. Estradiol markedly increased the satiating potency of intraduodenal infusions of Intralipid but not the satiating potency of L-phenylalanine (10 min infusions, 0.44 ml/min, 0.13 kcal/ml), which in male rats satiates via a CCK-independent mechanism. Estradiol had no significant effect in rats pretreated with the CCK-1 receptor antagonist Devazepide (1 mg/kg, ip). The effect of estradiol on intraduodenal Intralipid-induced satiation was mirrored by selective increases in the number of cells expressing c-Fos immunoreactivity in a circumscribed region of the nucleus tractus solitarius (NTS), just caudal to the area postrema (cNTS) but not elsewhere in the NTS or the hypothalamic paraventricular or arcuate nuclei. In addition, a significant proportion of cNTS c-Fos-positive cells also expressed ERalpha. These data provide behavioral and cellular evidence that estradiol-ERalpha signaling in cNTS neurons increases the satiating potency of endogenous CCK released in response to ingested lipid.
Asarian
Lori
L
Institute of Animal Science, ETH (Swiss Institute of Technology) Zürich, Schorenstrasse 16, Schwerzenbach, Switzerland. lasarian@ethz.ch
Geary
Nori
N
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008055:Lipids; D008297:Male; D010052:Ovariectomy; D010649:Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012527:Satiation / Q000187:drug effects*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*