Crf type 2 receptor mediates estradiol-induced increase in hypothalamic leptin sensitivity
P. Marangon, J. Antunes-Rodrigues & L. Elias
Energy homeostasis is controlled by neural, endocrine and adipocyte factors and CNS plays a key role in this control. We have previously observed that ovariectomized (OVX) rats treated with estradiol have lower body weight gain associated with an increased hypothalamic CRF mRNA expression. We investigated the role of CRF on activation of hypothalamic CART neurons by leptin in estradiol-treated OVX rats. Female Wistar rats (200250 g) were subjected to both OVX and cannula implantation into the lateral ventricle and treated with estradiol cypionate (OVX+E, 10 μg/kg Bw, s.c.) or vehicle (OVX, corn oil: 0.2 ml/rat, s.c.) for 8 days. I C V injection of recombinant leptin (10 μg/5 μμ) was performed with i c v pre-treatment with CRF-R2 antagonist (antisauvagin−30. 5 μg/5 μl) or vehicle. Anesthetized rats were perfused 90 min after leptin or vehicle injection. Fos/CART expressions were analyzed in the arcuate nucleus (ARC) of the hypothalamus by immunohistochemistry. Leptin induced body weight loss and reduced food intake both in OVX and OVX+E and increased neuronal activation in the ARC in OVX animals with this effect being amplified by estradiol treatment (OVX: 5.0±0.6 vs 17.8±2.7; OVX+E: 3.3±1.3 vs 28.3±6.1; n=3-5; P<0.05; vehicle vs leptin, respectively). These effects of leptin were abolished by CRF-R2 antagonist pre-treatment only in OVX+E rats (5.2±1.9; n=5; P<0.001). Leptin treatment increased Fos/CART double-labeling in the ARC in OVX and OVX+E animals (OVX: 1.7+0.9 vs 9.5+1.6; OVX+E: 0.3+0.3 vs 9.5+2.2; n=3-5; P<0.001), with no differences between these groups. CRF-R2 antagonist abolished leptin effect on Fos/CART double labeled neurons only in OVX+E rats (10.5+0.3; n=5; P<0.001). In conclusion, our data suggest that estradiol increases hypothalamic sensitivity to leptin and this central effect is mediated, at least in part, by CRF type 2 receptors.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.