**Part 2**

**Sex Steroids, Memory and the Brain** 

136 Sex Steroids

[120] Douglas, A.J. and J.A. Russell, *Endogenous opioid regulation of oxytocin and ACTH secretion during pregnancy and parturition.* Prog.Brain Res., 2001. 133: p. 67-82. [121] Russell, J.A., A.J. Douglas, and C.D. Ingram, *Brain preparations for maternity--adaptive* 

[122] Tilbrook, A.J., et al., *Activation of the hypothalamo-pituitary-adrenal axis by isolation and* 

[123] Cook, C.J., *Oxytocin and prolactin suppress cortisol responses to acute stress in both lactating* 

*and non-lactating sheep.* J.Dairy Res., 1997. 64(3): p. 327-339.

*overview.* Prog.Brain Res., 2001. 133: p. 1-38.

Endocrinology, 2006. 147(7): p. 3501-3509.

*changes in behavioral and neuroendocrine systems during pregnancy and lactation. An* 

*restraint stress during lactation in ewes: Effect of the presence of the lamb and suckling.*

**7** 

*USA* 

**Estrogen and Brain Protection** 

Xiaohua Ju, Daniel Metzger and Marianna Jung

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 non-

There are three major forms of endogenous estrogens; 17β-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, 17β-estradiol (Figure 1) is the most potent, naturally occurring estrogen. Accordingly, 17β-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.

Fig. 1. Chemical structures of 17β-estradiol, estriol, and estrone. Notice that 17β-estradiol has two hydroxyl (OH) groups, estriol has three hydroxyl groups, and estrone has one

**1. Introduction** 

genomic processes.

hydroxyl and one ketone group.

*University of North Texas Health Science Center* 
