The effects of peripherally administered 17‐beta estradiol and NPY Y1 receptor antagonist, BIBP3226, on food intake, body mass, reproductive organ development and behavior in leptin‐deficient mice.

Puberty in female mammals follows the accumulation of metabolic energy reserves in the form of adipose tissue. The balance between energy intake and expenditure depends on the cumulative influences of food intake, metabolic rate and locomotor activity. Energy balance is coordinated by counter‐regulatory anorexigenic and orexigenic signals that reduce and increase, respectively, the rate of food intake. Leptin, a potent anorexigenic signal secreted from active adipocytes, binds its targets in the arcuate nucleus of the hypothalamus to decrease activity of the major orexigenic signal, neuropeptide Y, thus attenuating appetite and increasing metabolism. The ob/ob phenotype in house mice is characterized by hyperphagia, pronounced obesity and infertility. To further elucidate the role of leptin in energy homeostasis and reproductive development in leptin‐deficient ob/ob mice, we evaluated the influence of exogenous estradiol and a neuropeptide Y receptor antagonist. We administered 17‐β estradiol and/or neuropeptide Y Y1 receptor antagonist, BIBP3226, twice daily for 14 consecutive days to peri‐pubertal female ob/ob mice. Food intake, body mass, reproductive behavior and vaginal opening were monitored. Following 13 days of treatment, ob/ob females were housed with stud males for 12 hours of behavioral testing. Immediately thereafter, the uterine and ovarian masses were determined, as was the presence or absence of sperm in the reproductive tract. Our data suggest that exogenous estradiol, even in the absence of leptin signaling, attenuates appetite, reduces body mass, promotes reproductive organ development, and increases reproductive behavior in ob/ob female mice. Statistical analyses are underway.