Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone.
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.
Tritos
Nicholas A
NA
Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Segal-Lieberman
Gabriella
G
Vezeridis
Peter S
PS
Maratos-Flier
Eleftheria
E
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*
D004041:Dietary Fats; D004343:Drug Implants; D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D010907:Pituitary Hormones; D004958:Estradiol; C019463:melanin-concentrating hormone