Developmental changes in plasma leptin and hypothalamic leptin receptor expression in the rat: peripubertal changes and the emergence of sex differences.
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.
Smith
J T
JT
School of Anatomy and Human Biology and The Western Australian Institute for Medical Research, The University of Western Australia, 35 Stirling Hwy Crawley, Perth, Western Australia, 6009, Australia.
Waddell
B J
BJ
D000818:Animals; D000831:Animals, Newborn; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D020738:Leptin / Q000097:blood* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012723:Sex; D012741:Sexual Maturation / Q000502:physiology*
D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin