Regulation of leptin gene expression and secretion by steroid hormones

Previous work has shown that 17 beta-estradiol is the primary ovarian signa l regulating body weight and adiposity, although its mechanisms of action r emain unclear. We hypothesized that 17 beta-estradiol could enhance leptin levels as a mechanism of its anorectic effects. Administration of 5 mu g 17 beta-estradiol subcutaneously (s.c.) for 2 days significantly elevated lep tin mRNA levels in adipose tissue as compared to vehicle controls (P < 0.00 3). A time-course administration of estrogen showed increased mRNA levels i n adipose tissue between 6 and 12 h after estrogen injection as compared to vehicle controls (P < 0.03). Corresponding to the increased leptin mRNA le vels at 6 and 12 h, elevated plasma leptin levels were observed at 12 h aft er estrogen administration as compared to controls (P < 0.05). Administrati on of progesterone (1 mg/rat) after estradiol injection did not enhance the elevated leptin mRNA levels in adipose tissue. Serum leptin levels from cy cling rats did not differ significantly between metestrous and proestrous a nimals. In conclusion, the present studies demonstrate that 17 beta-estradi ol can regulate leptin gene expression and secretion in the female rat, thu s providing a better understanding of the possible anorectic effect of estr ogens. (C) 1999 Elsevier Science Inc. All rights reserved.