Abnormal estrous cyclicity and behavioral hyporesponsiveness to ovarian hormones in genetically obese Zucker female rats

Obese Zucker female rats are infertile. The present study was designed to assess estrous cyclicity in adult, ovary-intact, lean and obese Zucker rats and to compare reproductive behaviors induced by exogenous steroid hormones in ovariectomized (ovx) lean and obese Zucker rats. The majority (90%) of obese rats had incomplete cycles in comparison with the normal, 4-day cycles displayed by lean Zucker rats. After ovariectomy, all rats were treated with estradiol benzoate (EB, 15-100 micrograms/kg) or EB plus progesterone (P, 2-20 mg/kg), and tested for sexual receptivity and proceptivity (PRO). At the highest EB dose, obese Zucker females displayed lordosis less frequently than lean rats (lordosis quotient, LQ, 8 +/- 6% vs. 32 +/- 13%, respectively). At the lowest doses of EB plus P, lean females were extremely receptive and proceptive (LQ = 93 +/- 4%, PRO = 6.2 +/- 2 bouts/min). Zucker obese females, in contrast, were only slightly receptive (LQ = 26 +/- 11%) and showed less PRO than lean rats (PRO = 2.4 +/- 0.6 bouts/min). Increasing the dose of either EB or P, administered in combination with the lowest dose of the other hormone, produced receptivity and PRO in obese Zucker females that were comparable with those observed in lean rats. Serum estradiol and P levels in ovx obese rats were either equivalent to or higher than those in the ovx lean rats when both were given the same doses of hormones. These data suggest that considerably higher doses and serum concentrations of EB and/or P are required to elicit robust lordosis and PRO in ovx obese Zucker than in lean rats. This behavioral hyporesponsiveness to sex steroid hormones may contribute to infertility in the obese Zucker female rat.