Progesterone and the Neural Mechanisms of Behavior

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Proposal Number: IBN-9511895 Principal Investigator: DeBold, Joseph F. Progesterone is an important steroid hormone for regulating many aspects of physiology and behavior. According to the classical approach, steroid hormones exert their effects by entering cells, binding with a receptor inside the cell, and then the steroid-receptor complex acts on specific sites on the chromosomes to change which proteins that cell is producing. This mechanism of action has been described in virtually every cell that responds to steroid hormones. However, it appears to be absent in the ventral midbrain. Dr. DeBold's previous studies have shown that a form of progesterone that cannot enter neurons is effective in altering behavior when administered in the midbrain but not in other steroid sensitive areas. Therefore, the primary focus of the proposed studies is to determine how progesterone is acting on neurons to influence behavior and the connectivity of these neurons. Dr. DeBold will identify the neurons containing these unique characteristics by labeling progesterone with a fluorescent tag and identifying the cell to which it binds and then using neurochemical procedures, characterize the type of cells containing these novel receptors. Using selective pharmacological agents, the role of other neurotransmitters in mediating progesterone actions will be established. These studies investigate novel effects of steroid hormones and will be extremely beneficial in understanding the physiology and pathophysiology of these essential molecules.