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 defi ciency induces hypophagia and loss of body fat, we hypothesized that MCH ne urons may represent a specific LHA pathway that, when inhibited, contribute s to the pathogenesis of certain anorexia syndromes. To test this hypothesi s, we measured behavioral, hormonal, and hypothalamic neuropeptide response s in two models of hyperestrogenemia in male rats, a highly reproducible an orexia paradigm. Whereas estrogen-induced weight loss engaged multiple syst ems that normally favor recovery of lost weight, the expected increase of M CH mRNA expression induced by energy restriction was selectively and comple tely 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.