We reported that leptin mRNA is developmentally regulated and hypothesized that local leptin expression is important for the maturation of the hypothalamic-pituitary system. Pituitary leptin mRNA levels were down-regulated in early postnatal male and female rats. We now show that pituitary leptin protein content and expression of the long (OBRb) and short (OBRa) leptin receptor isoforms in the pituitary and hypothalamus also undergo age-related changes. Tissue was dissected from male and female rats (postnatal days (PD) 4, 14, 22 and 60). Pituitary leptin protein was measured by RIA (Alpco) and leptin receptor mRNA levels were evaluated by semi-quantitative RT-PCR.
There were no sex differences in pituitary leptin content but values decreased from ~25ng/mg protein (PD4), to ~3.5ng/mg (PD60; p < 0.005). This age-related decline in leptin protein is similar to that seen previously for pituitary leptin mRNA. We also observed a developmental difference in the expression of OBRa and OBRb. In the pituitary of male and female rats OBRa mRNA levels were high after birth (PD4) but decreased (3 to 5 -fold; p < 0.01) by PD22 and were further reduced by PD60. In contrast, OBRb mRNA levels remained unchanged between PD4-60. Interestingly, hypothalamic OBRb mRNA levels increased significantly from PD4 to PD22 (p < 0.01). We conclude that pituitary leptin and OBRa levels are markedly down-regulated between PD4-60, suggesting a role for endogenous pituitary leptin during early postnatal development. (Funded by the CDA, NSHRF and IWK Health Center).
08 - 11 Apr 2002
British Endocrine Societies