We investigated the effects of lactation on diurnal changes in serum
leptin and hypothalamic expression of the
leptin receptor isoforms, Ob-Ra, -Rb, -Rc, -Re and -Rf in rats. In non-lactating rats, serum
leptin concentration was increased at night while hypothalamic
mRNA levels of Ob-Rb, -Rc and -Re decreased; by contrast, expression of Ob-Ra and Ob-Rf was unchanged at night. There were significant negative correlations between serum
leptin and
mRNA expression of Ob-Rb (P<0.001) and Ob-Re (P<0.05), which were independent of time of day. In lactating rats, the nocturnal rise in serum
leptin was attenuated. Daytime hypothalamic Ob-Rb
mRNA levels were significantly lower than in non-lactating controls, and the normal nocturnal decreases in expression of Ob-Rb, -Rc and -Re were lost. The relationship between serum
leptin and Ob-Re expression was not changed by lactation. Lactation had no effect on the expression of Ob-Ra
mRNA in the hypothalamus. Decreased daytime Ob-Rb expression could lead to reduced hypothalamic sensitivity to
leptin, and thus contribute to increased daytime appetite in lactating rats. Moreover, maintaining high levels of Ob-Re expression could, by increasing hypothalamic
leptin-binding protein concentration and reducing local
leptin bioavailability, further accentuate
hyperphagia. Thus, selective changes in expression of specific
isoforms of the
leptin receptor may contribute to the
hyperphagia of lactation in rats.