Estrogen and Brain Protection

In 1931, estrogen was originally discovered as a female sex hormone by Marrian and Butenandt (1931). Estrogen is responsible for maintaining female reproductive organs and functions. Beyond the effects on reproductive organs, the neuroprotective activities of estrogen have been identified by Simpkins et al. (1994) and thereafter by numerous other researchers (Viscoli et al., 2001). The simple classification of the mechanisms of estrogen is genomic and non-genomic processes. The genomic mechanisms of estrogen involve estrogen receptors located in DNA. Upon binding its receptors, estrogen stimulates the synthesis of a variety of neuro-modulatory proteins. A body of evidence indicates that estrogen receptors are not necessary for certain neuroprotective effects of estrogen. For example, estrogen scavenges harmful reactive free radical species (Dhandapani & Brann, 2002), inhibits apoptotic process (a certain type of cell death), and modulates signal transduction, all of which do not require nucleic estrogen receptors. Estrogen’s neuroprotective properties may be the end result of well-orchestrated genomic and nongenomic processes. There are three major forms of endogenous estrogens; 17┚-estradiol, estrone, and estriol based on the hydroxyl or ketone ligand attached to the C17 position of the rightmost ring (D ring). Among these estrogens, 17┚-estradiol (Figure 1) is the most potent, naturally occurring estrogen. Accordingly, 17┚-estradiol has been the subject for neuroprotective properties in major neurodegenerative disorders such as stroke, Alzheimer’s disease, Parkinson’s disease, and ethanol withdrawal, and thus a topic of this book chapter.