HYPOTHALAMIC CONTROL OF PUBERTY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：深入了解灵长类动物下丘脑控制促性腺激素释放的机制，并最终为青春期相关疾病提供新的诊断工具和治疗策略。 描述：青春期在正常年龄的开始是非常重要的，因为任何偏离同龄人年龄的行为都可能导致心理上的不安。此外，与性早熟和青春期延迟相关的疾病，以及许多起源于青春期或随青春期恶化的疾病，如多囊卵巢综合征、癫痫、自闭症和精神分裂症，是相当大的临床问题。出于这些原因，使用非人灵长类动物作为模型来研究控制青春期开始的机制至关重要，并且将有助于理解和管理人类临床病例。本研究的长期目标是研究下丘脑在控制青春期开始中的作用。本项目的目的是研究kisspeptin-54负责触发恒河猴青春期的假设。虽然以前，我们已经发现GABA能抑制的减少发生在青春期LHRH释放增加的时候，但是什么触发青春期的开始的问题仍然不清楚。最近的临床研究表明，GPR 54及其配体kisspeptin-54可能在人类青春期开始的机制中起重要作用。该研究将调查1）LHRH神经元对kisspeptin-54的敏感性是否随发育年龄而变化，2）青春期kisspeptin-54的增加是否独立于卵巢类固醇激素反馈系统，3）kisspeptin-54是否与青春期相关，以及4）青春期kisspeptin的增加是否先于青春期GABA释放的减少。将在不同发育年龄的雌性恒河猴中评估LHRH和kisspeptin-54从茎正中隆起的体内释放。从拟议的项目的结果将提供深入了解下丘脑控制灵长类动物促性腺激素释放的机制，并最终将导致一个新的诊断工具，以及与青春期相关的疾病的治疗策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To provide insight into the mechanisms through which the hypothalamus controls gonadotropin release in primates and ultimately will lead to a new diagnostic tool as well as to a treatment strategy for disorders associated with puberty. DESCRIPTION: The onset of puberty at the normal age is very important, as any deviation from peer age can result in psychological perturbation. Moreover, disorders associated with precocious and delayed puberty, and many diseases such as polycystic ovarian syndrome, epilepsy, autism, and schizophrenia that originate at or worsen with puberty, are considerable clinical concerns. For these reasons, investigations of the mechanisms controlling the onset of puberty, using the non-human primate as a model, are essential and would contribute to the understanding and management of human clinical cases. The long-term objective of this research is to investigate the role of the hypothalamus in the control of the onset of puberty. The objective of this project is to study the hypothesis that kisspeptin-54 is responsible for triggering puberty in the rhesus monkey. Although previously, we have found that the reduction in GABAergic inhibition occurs at the time of the pubertal increase in LHRH release, the question of what triggers the onset of puberty is still unclear. Recent clinical studies indicate that GPR54 and its ligand kisspeptin-54 may be important for the mechanism of the onset of puberty in humans. The proposed study will investigate 1) whether sensitivity of LHRH neurons to kisspeptin-54 changes with developmental ages, 2) whether the pubertal increase in kisspeptin-54 is independent from the ovarian steroid hormone feedback system, 3) whether kisspeptin-54 increases in association with puberty, and 4) whether the pubertal increase in kisspeptin precedes the pubertal reduction in GABA release. In vivo release of LHRH and kisspeptin-54 from the stalk-median eminence will be assessed in female rhesus monkeys at different developmental ages. Results from the proposed project will provide insight into the mechanisms through which the hypothalamus controls gonadotropin release in primates and ultimately will lead to a new diagnostic tool as well as to a treatment strategy for disorders associated with puberty.