Effects of exogenous gonadal steroids on leptin homeostasis in rats

Background: In humans, circulating concentrations of the hormone leptin, normalized to body fat mass, are significantly higher in females compared to males. This experiment was designed to determine whether the administration of exogenous androgen or estrogen would significantly alter the relationship between plasma leptin and fat mass in rats. Methods: In the first experiment, plasma leptin and retroperitoneal and parametrial (female)/epididymal (male) adipose tissue expression of leptin mRNA were measured in five male and five female 9.5-week-old Sprague-Dawley rats. In a second experiment, gonadectomized 10.5-week-old female Sprague-Dawley rats received 1 or 2 weeks of daily intraperitoneal injections (in oil) of 750 mg testosterone propionate, 2.5 μg of estradiol benzoate or vehicle. At 0, 1, and 2 weeks, plasma concentrations of leptin, fat pad weight of parametrial and retroperitoneal fat pads, and leptin mRNA expression by Northern blot in retroperitoneal fat pads were determined. Daily weight and food intake of animals were monitored throughout the study. Results: Circulating leptin concentrations per unit of fat pad mass and leptin mRNA expression normalized to actin mRNA were higher in gonadally intact female compared to male rats. Compared to placebo, estrogen administration decreased food intake and body weight, but had no significant effect on leptin mRNA expression or on circulating leptin concentration. Testosterone administration increased body weight and decreased expression of leptin mRNA (only after 2 weeks), but did not change food intake or circulating leptin concentration. Conclusions: Administration of estrogen did not affect either leptin expression or the circulating concentration of leptin. Administration of androgen decreased expression of leptin mRNA. However, even after 2 weeks of testosterone administration to gonadectomized females, plasma leptin concentration, corrected for fat pad weight, was higher in gonadectomized females than in intact males. Thus, sex steroid-associated changes in plasma leptin concentration and leptin mRNA expression are not sufficient to explain the observed sexual dimorphism in plasma leptin concentrations in rats.