Fig. 4: PHF6 deficiency in ^ILPHF6 cells impairs stress-induced cell activation and hormone release.

a Representative images of c-Fos (green) and DAPI (blue) staining in the pituitary under RS-, FS-, and 2MT-stress conditions, as well as basal conditions, in control and Phf6 cKO mice. White dotted lines indicate the IL. Scale bars, 100 μm. b-d Quantification of c-Fos-positive cells in the IL under RS (b), FS (c), and 2MT (d) stress conditions. Following stress exposure, Phf6 cKO mice showed a significant reduction in the number of c-Fos-positive cells in the IL compared to control mice (RS: n = 4 per group, FS: n = 3 per group under basal and n = 4 per group under stress; 2MT: n = 3 per group under basal and n = 4 per group under stress; * p < 0.05, ** p < 0.01, two-way ANOVA with Bonferroni’s multiple comparisons test). e Representative images of FosB (green) and DAPI (blue) staining in the pituitary under basal and RS-stress conditions in control and Phf6 cKO mice. White dotted lines indicate the IL. Scale bars, 100 μm. f Quantification of FosB-positive cells in the IL under RS-stress conditions. Following RS-stress exposure, Phf6 cKO mice showed a significant reduction in the number of FosB-positive cells in the IL compared to control mice (n = 4 per group, *** p < 0.001, two-way ANOVA with Bonferroni’s multiple comparisons test). g Experimental design for assessing stress-induced hormone release in control and Phf6 cKO mice. h Plasma concentrations of α-MSH, β-endorphin, and corticosterone were significantly reduced in Phf6 cKO mice compared to control mice following RS stress (Ctrl-base, n = 11; Ctrl-stress, n = 11; Phf6 cKO-base, n = 12; Phf6 cKO-stress, n = 12, * p < 0.05, two-way ANOVA with Bonferroni’s multiple comparisons test). The stress-induced increase in plasma ACTH levels was comparable in Phf6 cKO mice and control mice (Ctrl-base, n = 8; Ctrl-stress, n = 8; Phf6 cKO-base, n = 7; Phf6 cKO-stress, n = 8; p = 0.1238). Data are presented as mean ± SEM.