Hypothalamic melanin-concentrating hormone and estrogen-induced weight loss.
Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen.
Mystkowski
P
P
Department of Medicine, University of Washington and Veterans Affairs (VA) Puget Sound Health Care System, Seattle, Washington 98104, USA.
Seeley
R J
RJ
Hahn
T M
TM
Baskin
D G
DG
Havel
P J
PJ
Matsumoto
A M
AM
Wilkinson
C W
CW
Peacock-Kinzig
K
K
Blake
K A
KA
Schwartz
M W
MW
D054369:Agouti-Related Protein; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004343:Drug Implants; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology*
D054369:Agouti-Related Protein; D004343:Drug Implants; D004967:Estrogens; D006728:Hormones; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D010907:Pituitary Hormones; D011506:Proteins; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone; D003346:Corticotropin-Releasing Hormone