Hedgehog signaling in pituitary function

描述（由申请方提供）：下丘脑控制垂体功能的发育和解剖学中断导致严重的内分泌缺陷，导致许多人类疾病。我们的研究将探讨刺猬（Hh），发育形态，作为一种介质的垂体内分泌输出的行动。在目标#1中，我们试图描述垂体内分泌细胞对Hh活性破坏的反应。在斑马鱼可接近的幼虫阶段进行这些实验后，我们将确定成熟脑垂体中Hh活性中断的作用。目标#2的目标是描述 腹侧下丘脑中投射接触垂体内分泌细胞的细胞过程的hh反应细胞。目的#3是通过检查下丘脑中的Hh信号传导是否受渗透应激的影响来研究Hh信号传导是否参与生理表现，并确定改变的Hh信号传导是否影响渗透稳态。总的来说，这些研究将提供深入了解是否以及如何Hh作为一个中央调节器的垂体功能的脊椎动物。更好地了解介导下丘脑-垂体连接的分子机制，可以帮助诊断和治疗影响生育力，生长，能量稳态，盐和水平衡的疾病，这些疾病植根于垂体激素分泌不足或分泌过多。 公共卫生相关性：下丘脑控制垂体功能的发育和解剖学破坏导致严重的内分泌缺陷，导致许多人类医学疾病。我们的研究将探讨的行动，分泌蛋白刺猬，发育形态，作为一种介质的内分泌输出的垂体。为了帮助诊断和治疗影响生育力，生长，能量稳态以及盐和水平衡的疾病，我们的目标是更好地了解中枢垂体调节。

DESCRIPTION (provided by applicant): Developmental and anatomical disruption of the hypothalamic control of pituitary function leads to profound endocrine deficiencies responsible for a number of human medical conditions. Our studies will explore the actions of Hedgehog (Hh), a developmental morphogen, as a mediator of endocrine output by the pituitary. In Aim #1 we seek to characterize the response of pituitary endocrine cells to disrupted Hh activity. After performing these experiments in the accessible larval stage of zebrafish we will then identify the actions of disrupted Hh activity in the mature pituitary. The goal of Aim #2 is to characterize the Hh-responsive cells in the ventral hypothalamus that project cellular processes that contact endocrine cells in the pituitary. Aim #3 is to investigate whether Hh signaling is involved in physiological performance by examining whether Hh signaling in the hypothalamus is affected by osmotic stress, and to determine whether altered Hh signaling impacts osmotic homeostasis. Collectively, these studies will provide insight into whether and how Hh acts as a central regulator of pituitary function in vertebrates. An improved understanding of the molecular mechanisms mediating hypothalamic-pituitary connectivity could aid in the diagnosis and treatment of diseases impacting fertility, growth, energy homeostasis, and salt and water balance that are rooted in hypo- or hypersecretion of pituitary hormones. PUBLIC HEALTH RELEVANCE: Developmental and anatomical disruption of the hypothalamic control of pituitary function leads to profound endocrine deficiencies responsible for a number of human medical conditions. Our studies will explore the actions of the secreted protein Hedgehog, a developmental morphogen, as a mediator of endocrine output by the pituitary. To aid in the diagnosis and treatment of diseases impacting fertility, growth, energy homeostasis, and salt and water balance, we aim to provide a better understanding of central pituitary regulation.