Rapid steroidogenesis in the brain.

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DESCRIPTION (provided by applicant): Important behavioral and physiological changes occur on a timescale of minutes, yet the neuroendocrine mechanisms that underlie these fast changes are not well understood. Steroid hormones represent one group of candidate molecules for such rapid neural and behavioral effects. Although steroid hormones are powerful and pervasive neuromodulators, little is known about how steroid levels within the brain (neurosteroids) are regulated over rapid time periods. Narrowing the gap in understanding this entire class of neuromodulators will provide insight into how neurotransmitter systems and neurosteroids interact on a minute-by-minute basis. Preliminary clinical investigations have indicated that neurosteroid pathophysiologies are involved in disorders such as postpartum depression, pregnancy fatigue, and epilepsy. Thus, a greater appreciation of how neurosteroid levels change overtime may improve our understanding of social behavior, mental health and disease. In this proposal, characterizing the activity of steroidogenic enzymes in the brain, as well as in vivo measurement of brain steroid levels, are critical and complementary approaches toward understanding the neuromodulatory role of steroids and the function of steroid conversion by the brain. This proposal seeks to clarify how rapid changes in brain steroid levels contribute to changes in brain function and social behavior. In the zebra finch model, the proposed experiments will assess how singing behavior is related to rapid changes in both brain steroid levels in vivo and changes in steroidogenic enzyme activity. The proposed experiments will also examine rapid changes in brain steroid levels and steroidogenic enzyme activity during acute stress. Both humans and songbirds exhibit significant steroidogenesis from non-gonadal origins, including brain, and so these experiments provide an opportunity to improve our understanding of basic neurosteroid mechanisms.