title: Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone.
abstract: OBJECTIVE
  Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E2-induced anorexia.
  
  
  METHODS
  We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high-fat diet.
  
  
  RESULTS
  We confirmed E2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia. E2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2-induced anorexia. High-fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week.
  
  
  CONCLUSIONS
  The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.
authors.affiliation: Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Tritos
authors.forename: Gabriella
authors.initials: G
authors.lastname: Segal-Lieberman
authors.forename: Peter S
authors.initials: PS
authors.lastname: Vezeridis
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage*; D007028:Hypothalamic Hormones / Q000172:deficiency / Q000502:physiology*; D020738:Leptin / Q000172:deficiency / Q000502:physiology*; D008297:Male; D008543:Melanins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D010907:Pituitary Hormones / Q000172:deficiency / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D004343:Drug Implants; D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D010907:Pituitary Hormones; D004958:Estradiol; C019463:melanin-concentrating hormone