Regulation of adrenal development and function by the mother's skeleton

母亲骨骼对肾上腺发育和功能的调节

基本信息

批准号：
10366329
负责人：
Vijay K Yadav
金额：
$ 34.83万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10366329
关键词：
ARHGEF5 gene Ablation Acute Adrenal Cortex Adrenal Glands Adrenal Medulla Adrenal gland hypofunction Affect Aldosterone Anatomy Area Binding Biochemical Biological Biological Assay Biology Birth Blood Circulation Brain Catecholamines Cells Chronic Cognition Corticosterone Corticotropin Development Developmental Process Electrolytes Embryo Endocrine Glands Endocrinology Epinephrine Exhibits Feedback Genetic Glucocorticoids Goals Growth Hippocampus (Brain)Homeostasis Hormones Hydrocortisone In Vitro Injections Insulin Mineralocorticoids Molecular Molecular Genetics Monkeys Mothers Mus Mutant Strains Mice Osteocalcin Parents Perinatal mortality demographics Phenotype Physiological Physiological Processes Physiology Placenta Plasma Pregnancy Primates Process Production Regulation Renin Rodent Role Signal Transduction Skeleton Steroid biosynthesis Steroids Testing Testosterone Vertebrates Wild Type Mouse Zona Fasciculata Zona Glomerulosa adiponectin base blood pressure regulation bone experimental study gain of function gland development improved in vivo inhibitor/antagonist loss of function mouse genetics mouse model novel offspring peptide hormone postnatal receptor steroid hormone

项目摘要

PROJECT SUMMARY The overall goal of this Application is to improve our understanding of the genetic and molecular control of adrenal gland homeostasis by studying how osteocalcin originating from maternal skeleton, affects adrenal growth and steroidogenesis of the offspring during development and after birth. Specifically we intend to 1] Establish that maternal Ocn is necessary for proper adrenal gland development and function. We will also 2] Establish genetically and in vivo that osteocalcin favors adrenal gland growth and steroidogenesis by signalling directly in the adrenal cortices through its receptor Gpr158. A third purpose of this application is to determine with precision the temporal course of osteocalcin’s effect on the adrenal gland development/function and investigate how maternal osteocalcin affects this process in the offspring. We will use mouse genetic, molecular and biochemical assays to investigate the molecular bases of the cross-talk between bone and the adrenal gland through osteocalcin in the regulation of adrenal steroid production. Together, this application will significantly advance our understanding of adrenal development and physiology in bony vertebrates by describing a novel regulation of adrenal gland development and steroidogenesis, which originates from the mother and is biologically relevant since its absence can be lethal.

项目概要该应用程序的总体目标是提高我们对遗传和分子控制的理解通过研究源自母体骨骼的骨钙素如何影响肾上腺来维持肾上腺稳态具体来说，我们打算 1] 后代的生长和类固醇生成。确定母体 Ocn 对于肾上腺的正常发育和功能是必需的，我们还将 2] 在遗传和体内确定骨钙素通过信号传导有利于肾上腺生长和类固醇生成该应用的第三个目的是确定通过其受体 Gpr158 直接进入肾上腺皮质。精确地了解骨钙素对肾上腺发育/功能的影响的时间过程，以及我们将利用小鼠遗传来研究母体骨钙素如何影响后代的这一过程。分子和生化测定来研究骨和骨之间串扰的分子基础肾上腺通过骨钙素调节肾上腺类固醇的产生，这种应用将共同作用。显着增进我们对骨脊椎动物肾上腺发育和生理学的理解描述了肾上腺发育和类固醇生成的新调节，其起源于母亲，并且具有生物学相关性，因为它的缺失可能是致命的。