Joseph DeBold - US grants

Progesterone is an important steroid hormone for regulating many aspects of physiology. It also has a number of effects on behavior. The research findings from Dr. DeBold's previous NSF grant showed that progesterone can affect behavior through direct action on two specific sites in the brain, one in the forebrain and one in the midbrain. The primary objective of the present award is to determine how progesterone acts at its target site in the midbrain to influence behavior. Steroid hormones generally 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 the proteins that the cell synthesizes. This mechanism of action has been found in virtually every cell that responds to steroid hormones. In the midbrain, however, progesterone appears to have its effect through a different mechanism. A form of progesterone which cannot enter cells can be effective in the midbrain, although it is inactive elsewhere. The effect of progesterone on behaviorally-relevant actions via neuronal membranes will be tested. The specific protein which mediates this action will be determined. The proposed studies will demonstrate an alternative mechanism of action for one class of steroid hormones. This work will contribute to knowledge about how hormones act to regulate behavior.

Why are the two sexes different? The simple answer is steroid hormones. Steroid hormones stimulate cell growth, sexual differentiation, and also trigger the expression of sex-typical behaviors. One of their most important targets is the brain. Until recently, it was thought that steroids exerted their effects directly on gene expression by binding to receptors in the cell nucleus. It has recently become clear that steroids act through nongenomic mechanisms as well. These recent findings may necessitate a "paradigm shift" in the way research into reproduction is conducted because it seems that the mechanisms of steroid action are much more complicated than previously thought. At large scientific meetings, practitioners of various disciplines tend to interact with each other and do not necessarily become exposed to fast breaking developments that, although relevant to their work, involve unfamiliar methods and expertise. The purpose of this conference is to bring molecular investigators together with behavioral neuroscientists to promote collaborations that can capitalize on recent advances in our understanding of the mechanism of steroid hormone action.