Effects of exogenous gonadal steroids on leptin homeostasis in rats

Background: In humans, circulating concentrations of the hormone leptin, no rmalized 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 relationsh ip between plasma leptin and fat mass in rats. Methods: In the first experiment, plasma leptin and retroperitoneal and par ametrial (female)/epididymal (male) adipose tissue expression of leptin mRN A were measured in five male and five female 9.5-week-old Sprague-Dawley ra ts. In a second experiment, gonadectomized 10.5-week-old female Sprague-Daw ley rats received 1 or 2 weeks of daily intraperitoneal injections (in oil) of 750 mg testosterone propionate, 2.5 mu g of estradiol benzoate or vehic le. At 0, 1, and 2 weeks, plasma concentrations of leptin, fat pad weight o f parametrial and retroperitoneal fat pads, and leptin mRNA expression by N orthern 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 lep tin mRNA expression normalized to actin mRNA were higher in gonadally intac t female compared to male rats. Compared to placebo, estrogen administratio n decreased food intake and body weight, but had no significant effect on l eptin mRNA expression or on circulating leptin concentration. Testosterone administration increased body weight and decreased expression of leptin mRN A (only after 2 weeks), but did not change food intake or circulating lepti n concentration, Conclusions: Administration of estrogen did not affect either leptin expres sion or the circulating concentration of leptin, Administration of androgen decreased expression of leptin mRNA, However, even after 2 weeks of testos terone administration to gonadectomized females, plasma leptin concentratio n, corrected for fat pad weight, was higher in gonadectomized females than in intact males, Thus, sex steroid-associated changes in plasma leptin conc entration and leptin mRNA expression are not sufficient to explain the obse rved sexual dimorphism in plasma leptin concentrations in rats.