Intra-hypothalamic Estrogen Regulates HPA Axis Activity And Glucose Metabolism

Estradiol was thought to be involved in the role of sex difference in response to stress and energy metabolism. To investigate the possible integrate site and mechanism, we designed three sets of experiment. First, we observed the systemic and intrahypothalamic estradiol response to physical restraint stress in female rats. Interestingly, both the local estradiol concentration and aromatase expression in the PVN increased during the1-h stress. PVN ERβ, but not ERa mRNA expression was significantly elevated in proestrous animals.Second, we investigate intra-hypothalamic estrogenic effect on HPA axis activity on both basal and stress condition. Local estradiol and estrogen receptor a (ERa) agonist propylpyrazoletriol (PPT) infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (p<0.001) on basal condition. PPT increased stress induced CORT whereas ERβ agonist diarylpropiolnitrile (DPN) decrease it.In the third set of experiment we aimed to determine the acute obesity-independent effects of hypothalamic estrogen signaling on glucose metabolism. The administration of E2by microdialysis, either in the hypothalamic paraventricular nucleus (PVN) or in the ventromedial nucleus (VMH), increased plasma glucose in OVX animals. However, VMH not PVN E2induced endogenous glucose production. The hepatic sympathetic denervation blunted VMH estrogenic effect but have no effect on PVN E2regulation on glucose metabolism.To conclude, estrogen regulates HPA axis activity on different level via two receptors within PVN. It seems ERa increase whereas ERβ decrease the HPA response to stress. To be different with HPA axis regulation, estrogen modulates glucose metabolism via different nucleus within hypothalamus. PVN estrogen seems to decrease glucose uptake whereas VMH estrogen seems to increase glucose production.