Project III - Steroidal and Metabolic Mediation of Reproductive Behavior

暴露在睾酮(T)下的女性胎儿在生殖行为中会产生不同的结果 曝光时间和剂量的作用。产前T导致高胰岛素血症和功能性 绵羊的高雄激素血症，多囊卵巢综合征妇女的典型表现，发展为严重的 代谢和生殖功能障碍。产前经T处理的绵羊，暴露于T 30天的临界 时期是表型为雌性的，能够交配，但在性行为的数量和类型上有所不同 展出了。由于所有女性都接受了同样的产前T治疗，这些数据表明 出生后生活史影响行为结果，而不仅仅是产前暴露于经T治疗的T 绵羊会产生典型的行为，表现为摄取食物的动机增加，以及对食物相关的奖励感知增加 信号。这种目标导向行为的改变很可能是因为动物有 过量的胰岛素，导致新陈代谢改变，食物暗示的突出程度增加。动物们争相进入 食物，最终建立了一个社会等级。更高级别的T处理的雌性表现出更典型的男性 行为而不是控件。因此，接受T处理的雌性成人性行为的变化可能是由于 胎儿期T对新陈代谢的影响(改变食物的有益特性)与 可变地影响社会等级，对男性典型行为的倾向也是由 我们假设产前暴露于T会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路径。拟议中的实验将测试 出生后高胰岛素血症或高雄激素血症的缓解改变与目标相关的行为 具有繁殖力。我们将检验产前T治疗改变动机和报酬的假设 在发育期间和成人中对刺激的感知，2)生后雄激素和胰岛素的治疗 敏感性会改变对生殖和喂养刺激的动机和奖励反应，以及3)产前治疗 通过改变中脑边缘动机/奖励中的基因和蛋白表达来影响行为 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.