PHYSIOLOGY AND PATHOPHYSIOLOGY OF GROWTH HORMONE VARIANT

描述(由申请人提供)：应聘者和工作环境： 苏珊·E·柯克医学博士是一位训练有素的临床医生，她的 导师临床科学家发展奖将为 扩大她的临床和基础科学研究技能。目前，她 是弗吉尼亚大学的内科助理教授。 除了她自己的实验室，柯克博士还得到了 尤金·巴雷特博士的实验室(糖尿病教育研究主任 迈克尔·索纳博士(医学部主任)。此外, 弗吉尼亚大学拥有一位优秀的、最先进的将军 完成临床研究的临床研究中心。背景： 在怀孕期间，正常的胎盘会产生多种激素，包括 人绒毛膜生长抑素(HCS)，以前称为人胎盘 Lactogen或HPL)和生长激素基因家族的另一个成员-- 胎盘生长激素变异或GH-V。因为HCS在高密度下循环 与脑下垂体生长有大约85%的同源性 激素(GH)，在I型妊娠中看到的许多GH样生物效应 糖尿病妇女(微血管病变恶化)，均归因于GH- 类似于HCS的属性。这一提议的主要假设是GH-V，而不是 HCS是正常妊娠中存在的主要促生长素。它, 像脑下生长激素一样，能否a)影响脑下垂体分泌，b)刺激GH 受体信号转导，c)加速糖尿病的微血管改变，以及 D)可能在决定正常妊娠的宫内发育和 妊娠合并糖尿病。研究计划：将衡量 1)GH-V对大鼠垂体GH分泌的影响； 2)GH-V激活的信号转导通路；3)GH-V对血管内皮细胞生长的影响 小鼠肾小球结构。

DESCRIPTION (provided by applicant): Candidate and Environment: Susan E. Kirk, M.D. is a well-trained clinician whose application for a Mentored Clinical Scientist Development Award will provide the opportunity for her to expand her clinical and basic science research skills. Currently, she is an Assistant Professor in Internal Medicine at the University of Virginia. In addition to her own laboratory, Dr. Kirk has the support and use of the laboratories of Dr. Eugene Barrett (Director, Diabetes Education Research Center) and Dr. Michael Thorner (Chair, Department of Medicine). In addition, the University of Virginia maintains an excellent, state-of-the-art General Clinical Research Center for completion of clinical studies. Background: During Pregnancy, the normal placenta produces multiple hormones including human chorionic somatomammotropin (hCS, formerly termed human placental lactogen or hPL) and another member of the growth hormone gene family -- placental growth hormone variant or GH-V. Because hCS circulates at high concentrations and has approximately 85 percent homology to pituitary growth hormone (GH), many of the GH-like biologic effects seen with pregnant Type I diabetic woman (worsening of microvascular disease), are attributed to the GH- like properties of hCS. The major hypothesis of this proposal is the GH-V, not hCS, is the principal somatotropic agent present in normal pregnancy. It, like pituitary GH, can a) influence pituitary secretion, b) stimulate GH receptor signaling, c) accelerate microvascular changes of diabetes, and d) may play a role in determining intrauterine growth in normal pregnancy and pregnancy complicated by diabetes mellitus. Research Plan: will measure 1) the impact of GH-V on pituitary GH secretion in rats; 2) signal transduction pathways activated by GH-V; 3) the effect of GH-V on glomerular structure in mice.