Progesterone and the Neural Mechanisms of Behavior

建议编号：IBN-9511895首席研究员：德博尔德，约瑟夫·F·孕酮是一种重要的类固醇激素，用于调节生理和行为的许多方面。根据经典的方法，类固醇激素通过进入细胞，与细胞内的受体结合来发挥作用，然后类固醇-受体复合体作用于染色体上的特定位置，改变细胞产生的蛋白质。这种作用机制在几乎每一个对类固醇激素有反应的细胞中都有描述。然而，它似乎在腹侧中脑中缺失。德博尔德博士之前的研究表明，一种无法进入神经元的黄体酮在中脑给药时，可以有效地改变行为，但在其他类固醇敏感区域则不起作用。因此，拟议研究的主要重点是确定孕酮是如何作用于神经元以影响这些神经元的行为和连接的。德博尔德博士将通过用荧光标记黄体酮，并确定它与之结合的细胞，然后使用神经化学程序，确定包含这些新型受体的细胞的类型，从而识别出包含这些独特特征的神经元。利用选择性的药理学药物，将确定其他神经递质在调停黄体酮活动中的作用。这些研究调查了类固醇激素的新作用，并将对理解这些基本分子的生理学和病理生理学非常有益。

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.