Project III - Steroidal and Metabolic Mediation of Reproductive Behavior

项目 III - 生殖行为的类固醇和代谢调节

基本信息

批准号：
8142937
负责人：
THERESA M LEE
金额：
$ 32.21万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8142937
关键词：
Accounting Address Adult Affect Androgens Animal Model Animals Award Behavior Behavior Control Copulation Cues Data Development Dose Eating Eating Disorders Environment Estrus Exhibits Exposure to Feeding behaviors Female Fetus Financial compensation Food Functional disorder Gene Expression Gene Proteins Goals Gonadal Steroid Hormones Growth Health Human Hyperandrogenism Hyperinsulinism Infertility Insulin Intervention Mammals Masculine Mediation Metabolic Metabolic Control Metabolism Morphology Motivation Nervous system structure Neural Pathways Neuroanatomy Obesity Outcome Ovarian Pathway interactions Pattern Perception Perinatal Exposure Phenotype Predisposition Pregnancy Probability Property Puberty Public Health Reproduction Reproductive Behavior Rewards Risk Role Sex Behavior Sheep Signal Transduction Social Hierarchy Steroid Receptors Steroids Stimulus Syndrome Testing Testosterone Time Variant Ventral Tegmental Area Woman attenuation behavior influence critical period driving behavior feeding in utero insulin sensitivity life history male mesolimbic system neural circuit novel postnatal prenatal prenatal exposure programs protein expression reproductive reproductive development research study response reward circuitry

项目摘要

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.

暴露于睾丸激素（t）的雌性胎儿在生殖行为中产生可变的结果计时和暴露剂量的功能。产前T会引起高胰岛素血症和功能母羊中的超雄激素，典型的多囊卵巢综合征的女性代谢和生殖功能障碍。产前T处理的绵羊，暴露于T 30天的关键时期是表型女性的，能够交配，但性行为的数量和类型有所不同展出。因为所有女性都接受了相同的产前治疗，所以这些数据表明产后生活历史会影响行为结果，而不仅仅是产前暴露于T. t. t. 绵羊会产生典型的食物摄入动机和奖励感知的行为信号。目标指导行为的这种改变可能会发展，因为动物有过量的胰岛素，导致新陈代谢改变和食物提示的显着性。动物争夺食物，最终建立了社会等级制度。较高的T型T处理的女性表现出更多的男性典型行为比对照。因此，T处理女性的成人性行为的变化可能是产前T对代谢的影响之间的相互作用，从而改变了食物的奖励和可变影响社会等级制度，对男性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唇骨变化负责目标指导和有益行为的途径。建议的实验将测试是否高胰岛素血症或高雄激素的产后衰减改变目标指导的行为与繁殖。我们将测试产前T治疗的假设1）改变动力和奖励在发育和成年人中对刺激的感知，2）产后治疗雄激素和胰岛素敏感性将改变动力和奖励对生殖和喂养刺激的反应，3）产前治疗通过改变基因和蛋白质表达在中溶胶动机/奖励中影响行为电路。