Vol 4 n° 2 - Cerebral aspects of reproductive endocrinology
Past issues Contributors How to publish Contributions and comments Home
 
strogen  is  a  pleiotropic  hormone  that  acts beyond  the  scope  of  its  reproductive  functions  and exerts protective actions on multiple tissues including the  brain.  The  protective  actions  of  estrogen  carry tremendous implications for the promotion of health and   the   prevention   of   disease   in   postmenopausal women. Since the life span of women has increased from approximately  50  to  80  years,  but  the  age  of  the menopause remains at about 51 years, women may now live over three decades of their lives in a hypoestrogenic, postmenopausal state. The impact of prolonged hypo- estrogenicity is now a critical health concern, since we realize that these women may suffer from an increased vulnerability to a variety of diseases. Conversely, replace- ment with estrogen appears to act in the primary pre- vention  of  many  disease  processes,  including  neuro- degeneration. Estrogen, however, is not always beneficial, as high and unopposed levels may increase the risk for certain cancers in some women. Our challenge, therefore, is to design hormone replacement therapies that exert only beneficial effects in the body. To this end, we must gain a more complete understanding of the spectrum of estrogen’s actions and, more specifically, we must dissect the mechanisms that underlie its actions. The broad spectrum of estrogen’s actions includes sig- nificant protection of the brain and primary prevention against neurodegeneration. Clinical observations indi- cate  that  estrogen  replacement  in  postmenopausal women can (i) ameliorate cognitive dysfunction, and (ii) decrease the risk and delay the onset of degenerative conditions such as Alzheimer’s disease (AD) and stroke. 1 4 9 B a s i c   r e s e a r c h We now appreciate that estrogen is a pleiotropic gonadal steroid that exerts profound effects on the plasticity and cell survival of the adult brain. Over the past century, the life span of women has increased, but the age of the menopause remains constant. This means that women may now live over one third of their lives in a hypoestro- genic, postmenopausal state. The impact of prolonged hypoestrogenicity on the brain is now a critical health concern as we realize that these women may suffer an increased risk of cognitive dysfunction and neurodegen- eration due to a variety of diseases. Accumulating evi- dence from both clinical and basic science studies indicates that estrogen exerts critical protective actions against neuro- degenerative conditions such as Alzheimer’s disease and stroke. Here, we review the discoveries that comprise our current understanding of estrogen action against neuro- degeneration. These findings carry far-reaching possibili- ties for improving the quality of life in our aging popula- tion. Dialogues Clin Neurosci. 2002;4:149-162. Estrogen and neuroprotection: from clinical observations to molecular mechanisms Dena B. Dubal, PhD; Phyllis M. Wise, PhD Keywords: estrogen; estradiol; estrogen replacement therapy; menopause; stroke; cerebral ischemia; Alzheimer’s disease; cognition, brain injury; neuroprotection Author affiliations: Department of Physiology, University of Kentucky College of Medicine, Lexington, KY, USA (Dena B. Dubal, PhD); Division of Biological Sciences, University of California Davis, Davis, Calif, USA (Phyllis M. Wise, PhD) Address   for   correspondence:   Dr   Phyllis   M.   Wise,   Dean,   Division   of Biological  Sciences  University  of  California  Davis,  One  Shields  Avenue, Davis, CA 95616-8536, USA (e-mail: pmwise@ucdavis.edu) E