Effects of estrous cycle and steroid replacement on the expression of leptin and uncoupling proteins in adipose tissue in the rat

Among other actions, leptin has been suggested to increase energy expenditu re and to modulate the menstrual cycle. In fact, the main effect of leptin seems to be modulating the sympathetic nervous system and gonadotropin-rele asing hormone pulsatility. We investigated whether changes in the plasma st eroid concentrations during the estrous cycle and after ovariectomy and ste roid replacement can modulate plasma leptin levels, adipose tissue leptin m RNA expression, and some of the candidates for mediating energy expenditure (uncoupling proteins (UCP) 1, 2, and 3 mRNA) in white and brown adipose ti ssue. Rats in estrous cycle or ovariectomized vats with or without estradiol or p rogesterone replacement therapy for 18 days were studied. Plasma leptin, in sulin, estradiol and progesterone were measured with radio-immunoassays. Le ptin mRNA expression was measured in subcutaneous, periovarian and mesenter ic white adipose tissue and in interscapular brown adipose tissue. Expressi on of UCP 1, 2, and 3 mRNA in periovarian white and brown adipose tissue wa s analyzed. Plasma leptin levels were significantly decreased in the estrou s (1.1 +/- 0.4 ng/ml) compared with the pro-estrous (1.7 +/- 0.4 ng/ml, F = 3.0, p = 0.046) phase of cycle. UCP1 mRNA levels in brown adipose tissue w ere move elevated during pro-estrus than during metestrus (F = 3.17, p = 0. 039). Gene expressions of leptin, UCP2 or UCP3 mRNA did not change signific antly during the cycle. In ovariectomized rats, estradiol and/or progestero ne treatment had no effect on plasma leptin levels. Gene expression analysi s of leptin and UCP1, 2 and 3 in adipose tissue was not affected by steroid replacement. In conclusion, the estrous cycle appears to have a minor effect on modulati on of leptin and uncoupling proteins. Only plasma leptin levels and express ion of UCP1 mRNA are modestly elevated during the estrous cycle in the vat. Since estrogen and/or progesterone substitution in ovariectomized vats doe s not affect circulating leptin concentration or expression of leptin and U CPs in adipose tissue, it is unlikely that steroids play a major role in th eir regulation.