Melinda Wilson, PhD

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. Other projects in the laboratory involve deciphering the molecular mechanisms of how the estrogen receptor is regulated in a variety of physiological conditions. We have discovered that the estrogen receptor gene is regulated by epigenetic mechanisms during brain development and this can be modulated by injury in the adult brain. Furthermore, we have identified sex differences in this expression in the adult. As many of the actions of estrogen require the estrogen receptor, appropriate expression during development, aging and disease are all critical for estrogen action.

Current Teaching Activities:

PT 854   Pathophysiology, “Disorders of the Endocrine System”

PGY 431    Neuroendocrinology, Lecturer and Course Director

PGY 502    Principles of Systems, Cellular and Molecular Physiology, “Endocrine System”

PGY 602    Readings in Systems, Cellular and Molecular Physiology

PHA 424G    Pharmacology of the Human Endocrinology and Reproduction Endocrine and Reproductive Systems, Co-Course Director 

IBS 606     Physiological Communications, Course Director and “Neural Development”

MD 824    Endocrine and Reproductive Systems