Estrogen increases in vivo leptin production in rats and human subjects

Abstract

The decrease in estrogen in menopausal women increases body fat. The present studies were undertaken to investigate the involvement of estrogen in leptin production in vivo. In the first study, expression of ob gene mRNA in white adipose tissue was measured at 2 and 8 weeks after ovariectomy in rats. In the second, serum leptin concentration was measured in total body fat of 87 weight-matched human subjects (29 men, 29 premenopausal and 29 postmenopausal women). In the third, changes in serum leptin concentration with the menstrual cycle were determined. ob gene expression decreased in subcutaneous and retroperitoneal white adipose tissue of ovariectomized rats 8 weeks after the operation, while ovariectomy increased ob gene expression in mesenteric white adipose tissue. Serum leptin concentration was decreased by ovariectomy. Estradiol supplement reversed the effect of ovariectomy on ob gene expression and circulating leptin levels. In humans, serum leptin concentration was higher in premenopausal women than in men, and in postmenopausal women it was lower than in premenopausal women, but still higher than in men. In 13 premenopausal women, serum leptin levels were significantly higher in the luteal phase than in the follicular phase. The present studies strongly indicate that estrogen regulates leptin production in rats and human subjects in vivo. Regional variation in the regulation of ob gene expression by estrogen was found.

Gender difference in the leptin response to feeding in peroxisome-proliferator-activated receptor-alpha knockout mice

“…Studies in vitro and in vivo would suggest that sex steroids are directly responsible for the gender difference, with a direct inhibitory effect of testosterone on leptin in humans 18,19 and an increase in response to oestrogen in humans and rats. 20 Other researchers also show a higher leptin concentration in female mice, 21 however one study in rats has documented a reversal in the sexual dimorphism. 22 Leptin concentrations did not fall during this relatively shorting period of fasting, however we were able to demonstrate a rapid increase in concentrations within hours of refeeding, similar to that seen in other studies.…”

Circulating levels of leptin, adiposity and breast cancer risk

“…Circumstantial evidence suggests that ovarian hormones affect leptin production. Leptin is reported to fluctuate with the menstrual cycle (Shimizu et al, 1997), and premenopausal HRT may regulate leptin concentrations (Augoulea et al, 2005). However, our data indicated that there was no significant difference in the average duration between the date of last menstruation and the date of enrolment between premenopausal cases and controls (25.5 vs 26.5 days), and this average duration was not significantly associated with circulating leptin levels (the Spearman correlation coefficient in the control group was 0.0823; P ¼ 0.8361).…”

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

“…Ovariectomy in adult rats causes a significantly decline in circulating leptin concentrations that is reversed by estradiol supplementation. 24 Circulating plasma leptin concentrations, normalized to body mass index (BMI) (a surrogate indicator of fat mass), are significantly increased in hypogonadal compared to eugonadal men, and leptin concentrations are lowered in hypogonadal men following administration of testosterone. 25 Administration of estradiol and cyprotereone acetate (an androgen receptor antagonist) to transsexual males increases circulating plasma leptin concentration (160 -180%) while administration of testosterone to transsexual females increased body weight and decreases circulating leptin concentration (750 -60%).…”