Physiology

MELINDA E. WILSON, Ph.D. Associate Professor Ph.D. Loyola University Chicago, 1997 Office: MS-609A Medical Center 0298 Tel: (859) 323-9618 Fax: (859) 323-1070 Lab: MS-618 Tel (859) 323-7801 E-mail: mewils2@uky.edu Curriculum Vita (pdf)

The gonadal steroid hormone estrogen is essential for reproduction. It plays a critical role in the brain and the pituitary in regulating the sequence of hormonal events that result in female reproduction. In recent years, however, we have begun to appreciate that estrogen also exerts many critical effects on non-reproductive systems as well. Estrogen enhances cognition during normal aging as well as plays a protective role against a variety of neurodegenerative conditions. As our lifespan continues to increase, women are spending a greater proportion of their lives in a hypoestrogenic state. Thus, it is critical to understand the tissue-specific mechanisms of estrogen action to help design strategies of replacement that will provide protection in the brain without increasing potentially deleterious effects of long-term estrogen therapy in other tissues.

The actions of steroid hormones are mediated at the cellular level via intracellular receptors that act as transcription factors or indirectly modulate transcription by interacting with other signal transduction pathways. Thus, steroid hormone receptors provide an exciting opportunity to study physiology at the molecular level. My research focuses on the mechanisms by which estrogen acts to protect cells from injury. We utilize an in vitro organotypic explant culture model of the cortex. Explant cultures provide and excellent model in which to study neuronal responses in the presence of local communication with other neurons and glia. We have shown that in a receptor-dependent fashion, estrogen prevents apoptosis in cortical neurons by both suppressing pro-apoptotic signaling pathways and enhancing anti-apoptotic signaling pathways following injury. We are currently investigating how estrogen may protect the brain from HIV proteins. These proteins are secreted from infected non-neuronal cells in the brain causing neurotoxic injury and ultimately dementia.

Because of recent studies implicating hormone replacement therapy in adverse cardiovascular events, we are studying some of the differences in estrogen action in cells of the central nervous system and the cardiovascular system. An understanding of these differences will allow us to develop better strategies for hormone replacement.

A third project we have recently begun in the laboratory involves deciphering the mechanisms of how the estrogen receptor is regulated in a variety of physiological conditions. As many of the actions of estrogen require the estrogen receptor, appropriate expression in conditions of aging and disease are critical for estrogen action.

Recent Publications

Wilson, ME, Westberry, JM and Prewitt, AK. (2008) Dynamic Regulation of Estrogen Receptor-Alpha Gene Expression in the Brain: A Role for Promoter Methylation? Frontiers in Neuroendocrinology, 29: 378-385.

Westberry, JM, Prewitt, AK and Wilson ME (2008). Epigenetic regulation of the estrogen receptor alpha promoter in the cerebral cortex following ischemia in male and female rats. Neuroscience 152: 982-989.

Wilson, ME, Sengoku, T, Allred, KF (2008). Estrogen prevents cholesterol accumulation in macrophages induced by ritonavir. Journal of Cellular Biochemistry. 103: 1598-1606.

Wilson, ME, Allred, KF, Kordik, EM, Jasper, DK, Rosewell, AN, Bisotti, AJ (2007). Gender-specific effects of HIV protease inhibitors on body mass in mice. AIDS Research and Therapy 4:8.

Bruce-Keller AJ, Dimayuga, FO, Reed, JL, Wang, C, Angers, R, Wilson, ME, Dimayuga, VM, Scheff, SW, (2007). Gender and estrogen manipulation do not affect traumatic brain injury in mice. Journal of Neurotrauma, 24: 203-215.

Prewitt, AK and Wilson, ME (2007). Regulation of estrogen receptor-alpha in the developing mouse cortex. Brain Research 1134: 62-69.

Wilson, ME, Dimayuga, FO, Reed, JL, Curry, TE, Anderson, CF, Nath, A, Bruce-Keller, AJ. (2006) Immune Modulation by Estrogens: Role in CNS HIV-1 Infection. Endocrine 29:289-298.

Wilson, ME, Allred, KF, Bisotti, AJ, Chauhan, A, Bruce-Keller, AJ, Nath, A (2006). Estrogen suppresses Tat-induced transcription in glial cells. AIDS Research and Human Retroviruses 22: 350-356.

Allred, KF, Smart, EJ, Wilson, ME (2006). Estrogen receptor-alpha decreases HIV protease inhibitor-induced atherosclerosis. Journal of Biological Chemistry 281:1419-1425.

Other Publications