CREB1 and hyperinsulinemic hypoglycemia, familial, 4: In contrast, another study described more prominent amyloid plaques in the hippocampus of female 3xTg mice compared to male 3xTg mice, with estrogen deficiency-induced PKA-CREB-MAPK (protein kinase A-cAMP response element-binding protein and p38–mitogen-activated protein kinases) signaling disorder involved [44].