Hedgehog signaling in pituitary function

垂体功能中的 Hedgehog 信号传导

• 批准号: 8398037
• 负责人: Jason Breves
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2013-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8398037
• 关键词: Acute; Adult; Affect; Anterior Pituitary Hormones; Behavior; Cell Proliferation; Cell physiology; Cells; Data; Development; Diagnosis; Diagnostic Procedure; Disease; Endocrine; Equilibrium; Erinaceidae; Exhibits; Fertility; Fishes; Gene Expression; Gene Expression Regulation; Gene Proteins; Genes; Genetic Transcription; Gills; Goals; Growth; Homeostasis; Hormones; Human; Hypothalamic structure; Ions; Larva; Link; Mammals; Maps; Mediating; Mediator of activation protein; Medical; Mitogens; Molecular; Nervous system structure; Neuroglia; Neurosecretory Systems; Organism; Osmoregulation; Output; Pathway interactions; Patients; Pattern; Performance; Physiological; Pituitary Gland; Pituitary Hormones; Plant Roots; Play; Population; Pro-Opiomelanocortin; Prolactin; Prosencephalon; Proteins; Regulation; Role; Signal Transduction; Sodium Chloride; Somatotropin; Staging; Stem cells; Stress; Therapeutic Agents; Transgenic Organisms; Vertebrates; Water; Zebrafish; cell type; cyclopamine; embryo tissue; experience; hypothalamic pituitary axis; improved; insight; lactotroph; morphogens; novel; novel diagnostics; protein expression; research study; response; smoothened signaling pathway; teleost

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.

描述(由申请人提供)：下丘脑对垂体功能的发育和解剖控制障碍导致严重的内分泌缺陷，导致许多人类医学疾病。我们的研究将探索刺猬(Hedgehog，HH)作为脑下垂体内分泌输出的中介物的作用。在目标#1中，我们试图描述垂体内分泌细胞对HH活性中断的反应。在斑马鱼可接近的幼体阶段进行这些实验后，我们将确定成熟脑垂体中HH活性被破坏的行为。目标2的目标是描述 下丘脑腹侧的HH反应细胞，投射细胞突起，与垂体腺的内分泌细胞接触。目的#3是通过检测下丘脑中的HH信号是否受到渗透压的影响来研究HH信号是否参与生理活动，并确定HH信号的改变是否影响渗透平衡。总而言之，这些研究将提供关于HH是否以及如何作为脊椎动物脑垂体功能的中央调节器的洞察力。对调节下丘脑-垂体连接的分子机制的深入了解有助于诊断和治疗影响生育、生长、能量平衡和盐水平衡的疾病，这些疾病根源于垂体激素的低分泌或高分泌。 公共卫生相关性：下丘脑对垂体功能控制的发育和解剖障碍导致严重的内分泌缺陷，导致许多人类医疗状况。我们的研究将探索分泌蛋白Hedgehog的作用，Hedgehog是一种发育形态生成素，作为脑垂体内分泌输出的中介。为了帮助诊断和治疗影响生育、生长、能量平衡和盐水平衡的疾病，我们的目标是更好地了解中枢垂体调节。

项目成果

Nutritional status and growth hormone regulate insulin-like growth factor binding protein (igfbp) transcripts in Mozambique tilapia.

• DOI: 10.1016/j.ygcen.2014.04.034
• 发表时间: 2014-10-01
• 期刊: GENERAL AND COMPARATIVE ENDOCRINOLOGY
• 影响因子: 2.7
• 作者: Breves, Jason P.;Tipsmark, Christian K.;Stough, Beth A.;Seale, Andre P.;Flack, Brenda R.;Moorman, Benjamin P.;Lerner, Darren T.;Grau, E. Gordon
• 通讯作者: Grau, E. Gordon