Estrogenic regulation of memory consolidation: A look beyond the hippocampus, ovaries, and females

The potent estrogen 17 beta-estradiol (E-2) has long been known to regulate the hippocampus and hippocampal-dependent memories in females, and research from the past decade has begun to shed light on the molecular mechanisms through which E-2 mediates memory formation in females. Although E-2 can also regulate hippocampal function in males, relatively little is known about how E-2 influences memory formation in males, or whether sex differences in underlying mechanisms exist. This review, based on a talk given in April 2017 at the American University symposium entitled, Sex Differences: From Neuroscience to the Clinic and Beyond, first provides an overview of the molecular mechanisms in the dorsal hippocampus through which E-2 enhances memory consolidation in ovariectomized female mice. Next, newer research is described demonstrating key roles for the prefrontal cortex and de novo hippocampal E-2 synthesis to the memory-enhancing effects of E-2 in females. The review then discusses the effects of de novo and exogenous E-2 on hippocampal memory consolidation in both sexes, and putative sex differences in the underlying molecular mechanisms through which E-2 enhances memory formation. The review concludes by discussing the importance and implications of sex differences in the molecular mechanisms underlying E-2-induced memory consolidation for human health.