Novel Mechanistic Targets of Steroid Hormones in the Brain

The Program Project has the overall goal of identifying novel mechanistic targets of estrogen and progesterone in the brain. This program of research is driven by a critical need to improve our understanding of gonadal hormone neurobiology, a need that became evident following the unexpected results from the Women’s Health Initiative Memory Study that identified negative effects of hormone therapy, in contrast to prior studies that supported a benefit.

To address this need, we have organized a program of research that consists of 4 research projects, 2 supporting core facilities, and a group of talented investigators. The projects explore important, novel targets of estrogen and progesterone that are relevant for neuroprotection and brain plasticity.

Project 1 focuses on the recently identified membrane progesterone receptor (mPR) as an important mediator of progesterone’s protective effects in the brain.
PI: Meharvan Singh, PhD
Project 2 capitalizes on the discovery of the mitochondrial estrogen receptor-? (ER?), and proposes this as a key molecule in regulating the vulnerability of neurons to age-related insults.
PI: James Simpkins, PhD
Project 3 emphasizes the role of the intracellular calcium channels, the IP3 and ryanodine receptors, as important mediators of both estrogen- and progesterone-induced neuroprotection.
PI: Peter Koulen, PhD
Administrative Core (Core A) oversees the program of research, provides biostatistical support, and data management. Project1singh
Animal Core (Core B) oversees the common animal model (ovariectomized animals that have undergone transient cerebral ischemia).

Tissue Bank Various tissues will become available.

This multi-disciplinary program of research will not only enhance our understanding of the neurobiology of estrogens and progestins but will lead to the discovery of new and important molecules to which future drug discovery efforts may target for the development of effective means of treating/preventing brain dysfunction associated with age or age-related disorders like Alzheimer’s Disease.