Physiologic estradiol levels enhance hypothalamic expression of the long form of the leptin receptor in intact rats.
Estradiol is a potent hypophagic agent that reduces food intake and body weight without a concomitant fall in plasma leptin levels. We investigated whether the hypophagic effect of estradiol is mediated by stimulating POMC and/or inhibiting NPY neuronal pathways in the hypothalamus, which respectively inhibit and stimulate feeding. We examined hypothalamic gene expression of Ob-Rb, NPY, POMC, MC4-R, and AgRP in intact Wistar rats treated with estradiol for 48 hours. Food intake and body weight were reduced in estradiol-treated rats but fat mass was unchanged; plasma leptin and insulin levels were not significantly different from untreated, freely fed controls. In untreated rats that were pair-fed to match the estradiol-treated group, body weight was also reduced without changes in fat mass, although leptin and insulin levels decreased significantly. Ob-Rb expression was increased in both hypophagic groups despite serum leptin were only decreased in pair-fed animals, suggesting an estradiol-stimulating effect on Ob-Rb expression. No significant differences were found in POMC, AgRP, or MC4-R expression among any of the experimental groups. A significant but small decrease in NPY expression was also found in both hypophagic groups; this was explained by the combined effect of both surgery and reduced food intake. These results indicate that estradiol mediated hypophagia in intact rats could be brought about by an enhanced hypothalamic leptin sensitivity but is unlikely to be driven by changes in NPY or melanocortin system.
Rocha
Milagros
M
Department of Physiology (Animal Physiology II), Faculty of Biological Sciences, Complutense University, 28040 Madrid, Spain.
Bing
Chen
C
Williams
Gareth
G
Puerta
Marisa
M
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004958:Estradiol / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009479:Neuropeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D004958:Estradiol