Abstract
The female sex hormone estrogen has a variety of metabolic activities including numerous effects on neurons. Therefore, the picture has changed from estrogen being a pure female sexual hormone important for sex differentiation and maturation to estrogen as a neuromodulator and neuroprotectant. It appears that estrogen specifically maintains verbal memory in women and may prevent the deterioration in short-and long-term memory that is associated with normal aging (Sherwin, 1999). Several epidemiological studies reported that estrogen replacement therapy of postmenopausal women may prevent neurodegenerative disorders including Alzheimer’s disease (Henderson, 1997). In addition, estrogen is not restricted to females since the male sex hormone testosterone (and other steroids with a 19 carbon atom structure, so-called C-19 steroid) can be chemically converted to estradiol in various tissues, including the brain, by an aromatase P450 enzyme (Schumacher et al., 2002). Many lines of evidence suggest that estrogen has neurotrophic and neuroprotective properties (Wise, 2002; Garcia-Segura et al., 2001). 17 ß-estradiol (ßE2) is a steroid hormone produced mainly in the ovaries, by the placenta during pregnancy, and to a lesser extent in the adrenal cortices, testes, and peripheral tissues (Schumacher et al., 2002). It is synthesized enzymatically from acetate, cholesterol, progesterone, and testosterone (Schumacher et al., 2002). For many years, it has been known that ßE2 promotes viability and survival of neurons in primary neuronal cultures. Addition of ßE2 to defined culture media increased the viability, survival and differentiation of primary neuronal cultures from different brain areas including amygdala (Lorenzo et al., 1992), hypothalamus (Cambiasso and Carrer, 2001), neocortex (Vedder et al., 1999). However, the role of estrogen in the protection of retinal neurons is unknown. We have previously established H202-induced cell death of cultured retinal neurons as a model system for studying stress-induced degeneration, and used this model
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Sherwin, B. B., 1999, Can estrogen keep you smart? Evidence from clinical studies, J Psychiatry Neurosci 24, 315–321.
Henderson, V. W., 1997, The epidemiology of estrogen replacement therapy and Alzheimer’s disease, Neurology 48, 27–35.
Schumacher, M., Akwa, Y., Guennoun, R., Robert, F., Labombarda, F., Desamaud, F., Robel, P., Nicola, A. F., and Baulieu, E. E., 2002, Steroid synthesis and metabolism in the nervous system: trophic and protective effects, J Neurocytol 29, 307–26.
Wise, P. M., 2002, Estrogens and neuroprotection, Trends Endocrinol Metab 13, 229–230.
Garcia-Segura, L. M., Azcoitia, I., and DonCarlos, L. L., 2001, Neuroprotection by estradiol, Prog Neurobiol. 63, 29–60.
Lorenzo, A., Diaz, H., Carrer, H., and Caceres, A., 1992, Amygdala neurons in vitro: neurite growth and effects of estradiol, J Neurosci Res 33, 418–435.
Cambiasso, M. J., and Carrer, H. F., 2001, Nongenomic mechanism mediates estradiol stimulation of axon growth in male rat hypothalamic neurons in vitro, J Neurosci Res 266, 475–481.
Vedder, H., Anthes, N., Stumm, G., Wurz, C., Behl, C., and Krieg, J. C., 1999, Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system, J Neurochem 72(6), 2531–2538.
Cao, W., Tombran-Tink, J., Chen, W., Mrazek, D., Elias, R., and McGinnis, J. F., 1999, Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death, J Neurosci Res 57, 789–800.
Rajala, R. V., and Anderson, R. E., 2001, Interaction of the insulin receptor beta-subunit with phosphatidylinositol 3-kinase in bovine ROS, Invest Ophthalmol Vis Sci 42, 3110–3117.
Honda, K., Shimohama, S., Sawada, H., Kihara, T., Nakamizo, T., Shibasaki, H., and Akaike, A., 2001, Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons, J Neurosci Res 64, 466–475.
Gallaher, B. W., Hille, R., Raile, K., and Kiess, W., 2001, Apoptosis: live or die--hard work either way, Horm Metab Res 33, 511–519.
Green, P. S., Yang, S. H., Nilsson, K. R., Kumar, A. S., Covey, D. F., and Simpkins, J. W., 2001, The nonfeminizing enantiomer of 17beta-estradiol exerts protective effects in neuronal cultures and a rat model of cerebral ischemia, Endocrinology 142, 400–406.
Dhandapani, K. M., and Brann, D. W., 2002, Protective effects of estrogen and selective estrogen receptor modulators in the brain, Biol Reprod 67, 1379–1385.
Singer, C. A., Rogers, K. L., Strickland, T. M., and Dorsa, D. M., 1996, Estrogen protects primary cortical neurons from glutamate toxicity, Neurosci Lett 212, 13–16.
Fitzpatrick, J. L., Mize, A. L., Wade, C. B., Harris, J. A., Shapiro, R. A., and Dorsa, D. M., 2002, Estrogen-mediated neuroprotection against beta-amyloid toxicity requires expression of estrogen receptor alpha or beta and activation of the MAPK pathway, J Neurochem 82, 674–682.
Richards, R. G., Walker, M. P., Sebastian, J., and DiAugustine, R. P., 1998, Insulin-like growth factor-1 (IGF1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse, J Biol Chem 273, 11962–11969.
Gosbell, A. D., Favilla, I., Baxter, K. M., Jablonski, P., 2000, Insulin receptor and insulin receptor substrate-I in rat retinae, Clin Experiment Ophthalmol 28, 212–215.
Barber, A. J., Nakamura, M., Wolpert, E. B., Reiter, C. E., Seigel, G. M., Antonetti, D. A., and Gardner, T. W., 2001, Insulin rescues retinal neurons from apoptosis by a phosphatidylinositol 3-kinase/Akt-mediated mechanism that reduces the activation of caspase-3, J Biol Chem 276, 32814–32821.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this paper
Cite this paper
Cao, W. et al. (2003). Neuroprotective Effect of Estrogen upon Retinal Neurons in Vitro. In: LaVail, M.M., Hollyfield, J.G., Anderson, R.E. (eds) Retinal Degenerations. Advances in Experimental Medicine and Biology, vol 533. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0067-4_50
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0067-4_50
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4909-9
Online ISBN: 978-1-4615-0067-4
eBook Packages: Springer Book Archive