Developmental changes in plasma leptin and hypothalamic leptin receptor expression in the rat: peripubertal changes and the emergence of sex differences

Abstract

Leptin, the peptide hormone product of the ob gene, regulates food intake and energy expenditure at the hypothalamic level via the long-form of the leptin receptor (Ob-Rb). Leptin also plays a key role in determining the onset of puberty, but there is controversy as to whether leptin provides a trigger for puberty or is a permissive signal. Thus, although leptin administration can advance puberty onset in rodents, circulating leptin appears stable across puberty. While these data suggest a permissive role for leptin in rat puberty, it is possible that a change in hypothalamic response to leptin (e.g. via increased Ob-Rb expression) could enhance leptin action and thus trigger puberty without a rise in circulating leptin. In the present study we assessed developmental changes in hypothalamic Ob-Rb mRNA and protein expression in female and male rats from late fetal to postpubertal life. Quantitative RT-PCR showed that Ob-Rb mRNA increased (P<0·05) by around fivefold from fetal to postpubertal life in both females and males. These increases in Ob-Rb mRNA expression were gradual, but did not increase significantly between postnatal day 30 (pre-puberty) and day 51 (post-puberty). By day 51, hypothalamic Ob-Rb mRNA expression was higher (P<0·05) in females relative to males. Hypothalamic Ob-Rb protein showed a comparable developmental pattern (approximate threefold increase from fetal to postpubertal life), although a significant increase (15%; P<0·05) was observed between days 30 and 51 in females. Plasma leptin levels exhibited a dynamic pattern in both male and female rats during the prepubertal period, characterised by a precipitous fall after birth, relative stability to day 5, then a rapid increase to a transient peak on day 12. Plasma leptin then remained unchanged from day 15 in female rats but increased in males after puberty, thus confirming the well-recognised sex difference in adult rat leptin levels. In conclusion, this study shows that developmental increases occur not only in plasma leptin but also in hypothalamic Ob-Rb expression, suggesting that both are likely to influence the timing of puberty onset. Moreover, our data show that sex differences in both hypothalamic Ob-Rb and plasma leptin emerge only after puberty.

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

“…It has been previously reported that both leptin and LEPR con- centrations/expression differ by sex, with females having larger amounts than males (71)(72)(73). Humans homozygous for 223R have been found to have significantly lower levels of LEPR expression; however, differences in expression due to sex were not reported (4).…”

The effect of a phytoestrogen, genistein, on the hormonal and metabolic status of pregnant rats

“…Recently, the function of the adipocyte-derived hormone, leptin, as a factor regulating food intake and energy expenditure has been widely investigated. Moreover, leptin plays an important role in the regulation of several processes associated with reproduction: puberty onset, ovarian function and fetal/ placental growth (Smith and Waddell, 2003). The leptin concentration increases throughout rodent gestation.…”

Developmental increases in plasma leptin binding activity and tissue Ob-Re mRNA expression in the rat

“…While the placenta is the major source of this binding activity in pregnancy (Gavrilova et al 1997, its source and variability in non-pregnant animals is unknown. Recently, we demonstrated that hypothalamic Ob-Rb expression increases progressively from the late fetal to the peripubertal period in both sexes (Smith & Waddell 2003a). These data suggest that enhanced responsiveness of the hypothalamus to leptin may contribute to puberty onset, but whether plasma leptin binding activity also changes during development, particularly in the peripubertal period, is unknown.…”