Project III - Steroidal and Metabolic Mediation of Reproductive Behavior

暴露于Tetrahydroxide（T）的雌性胎儿在生殖行为方面产生不同的结果， 曝光时间和剂量的函数。产前T导致高胰岛素血症和功能性 多囊卵巢综合征的典型表现是 代谢和生殖功能障碍。产前T处理的绵羊，暴露于T 30天的关键 在表型上是雌性，能够交配，但在性行为的数量和类型上有所不同 展出。由于所有女性都暴露于相同的产前T治疗，这些数据表明， 出生后的生活史影响行为结果，而不仅仅是产前接触T。产前T治疗 绵羊产生典型增加食物摄入动机和食物相关奖励感知的行为 信号.这种目标导向行为的改变可能是因为动物 过量的胰岛素，导致新陈代谢改变和食物线索的显著性增加。动物们争相进入 食物，最终建立社会等级制度。等级较高的T处理雌性动物表现出更多的雄性典型 行为比控制。因此，T-处理的雌性成年性行为的变化可能是一个结果， 产前T对新陈代谢的影响之间的相互作用，改变了食物的奖励特性， 性别影响社会等级，倾向于男性典型行为的倾向也是由 产前T.我们假设产前T暴露直接或间接导致中脑边缘改变， 负责目标导向和奖励行为的途径。拟议的实验将测试是否 出生后高胰岛素血症或高雄激素血症的减弱改变了与 与繁殖。我们将检验产前T治疗改变动机和奖励的假设 在发育过程中和成年人的刺激感知，2）出生后雄激素和胰岛素治疗 敏感性将改变对生殖和喂养刺激的动机和奖励反应，3）产前T治疗 通过改变中脑边缘动机/奖励中的基因和蛋白质表达来影响行为 电路

Female fetuses exposed to Testosterone (T) produce variable outcomes in reproductive behavior as a function of the timing and dose of exposure. Prenatal T causes hyperinsulinemia and functional hyperandrogenism in ewes, typical of women with polycystic ovarian syndrome who develop severe metabolic and reproductive dysfunction. Prenatal T-treated sheep, exposed to T for 30 days of a critical period are phenotypically female, capable of copulation, but vary in the amount and type of sex behavior exhibited. Because all females were exposed to the same prenatal T treatment, these data suggest that postnatal life history influences behavioral outcomes, not just prenatal exposure to T. Prenatal T-treated sheep produce behavior typical of increased motivation for food intake and reward perception for foodassociated signals. This alteration in goal-directed behavior likely develops because the animals have excess insulin, leading to altered metabolism and increased salience of food cues. Animals vie for access to food, eventually establishing a social hierarchy. Higher ranking T-treated females exhibit more male-typical behavior than controls. Thus, the variation in adult sex behavior of T-treated females may be the result of an interaction between the effects of prenatal T on metabolism, which alters rewarding properties of food and variably influences social hierarchy, with the predisposition towards male-typical behavior also caused by prenatal T. We hypothesize that prenatal T exposure leads directly or indirectly to altered mesolimbic pathways responsible for goal-directed and rewarding behaviors. Proposed experiments will test whether postnatal attenuation of hyperinsulinemia or hyperandrogenism alters goal-directed behaviors associated with reproduction. We will test the hypotheses that prenatal-T treatment 1) alters motivation and reward perception of stimuli during development and in adults, 2) that postnatal treatment of androgenic and insulin sensitivity will alter motivation and reward responses for reproductive and feeding stimuli, and 3) prenatal Ttreatment affects behavior by altering gene and protein expression in the mesolimbic motivation/reward circuitry.