Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats.
17beta-estradiol (E2), acting via estrogen receptor (ER)-alpha, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERalpha-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 microg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of (3)H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERalpha-positive cells in the cNTS after ip injection of 4 microg/kg CCK-8. We conclude that E2, acting via ERalpha in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.
Thammacharoen
Sumpun
S
Institute of Animal Science, Physiology and Behaviour Group, ETH-Zürich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Lutz
Thomas A
TA
Geary
Nori
N
Asarian
Lori
L
D000818:Animals; D001835:Body Weight; D002766:Cholecystokinin / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004435:Eating / Q000187:drug effects*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000032:analysis*; D005260:Female; D010052:Ovariectomy; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D012249:Rhombencephalon / Q000187:drug effects*; D017552:Solitary Nucleus / Q000737:chemistry / Q000187:drug effects*
D016207:Cytokines; D047628:Estrogen Receptor alpha; D016760:Proto-Oncogene Proteins c-fos; D004958:Estradiol; D002766:Cholecystokinin