Fig. 1
Chronic activation of CRHPVN neurons promotes tumor progression through the excess secretion of glucocorticoids. A Schematic images of the specific activation of CRHPVN neurons by the injection of AAV-derived transgenes into the PVN of CRH-ires-Cre mice. Schematic illustrations of CRH-ires-Cre mice (A-i), AAV injection site (A-ii) and AAV10-hSyn-Flex-hM3Dq-mCherry vector (A-iii). B Representative images of biocytin-labeled patched neuron and hM3Dq-mCherry in the PVN. Cell with blue (biocytin), red (hM3Dq-mCherry), and purple (merged) fluorescence. Voltage trace recorded from an hM3Dq-mCherry expressing CRH neuron during the application of CNO (3 μM) in a slice including the PVN. C Experimental schedule for evaluating tumor growth by the activation of CRHPVN neurons. D Quantitative analysis of tumor volume in WT/hM3Dq mice and CRH-Cre/hM3Dq mice. The results are presented as the mean ± S.E.M. The data were subjected to a comparative analysis by two-way ANOVA followed by the Bonferroni test: *p < 0.05, ***p < 0.001 vs. WT/hM3Dq mice (n = 22). E Plasma levels of corticosterone as measured by ELISA. Data are presented as the mean ± S.E.M. Unpaired t-test: *p < 0.05 vs. WT/hM3Dq mice (n = 16). F Experimental schedule for evaluating tumor growth by chronic exposure to hydrocortisone. G Quantitative analysis of tumor volume in the vehicle group and hydrocortisone group (10 mg/kg). Data are presented as the mean ± S.E.M. The data were subjected to a comparative analysis by two-way ANOVA followed by the Bonferroni test: *p < 0.05, ***p < 0.001 vs. vehicle group (n = 6)