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

项目摘要 本申请的总体目标是提高我们对以下遗传和分子控制的理解： 通过研究来自母体骨骼的骨钙素如何影响肾上腺的稳态， 在发育过程中和出生后后代的生长和类固醇合成。具体而言，我们打算1） 确定母体OCN对肾上腺正常发育和功能是必要的。我们也将[2] 在遗传和体内证实骨钙素通过信号传导促进肾上腺生长和类固醇生成 通过其受体Gpr 158直接作用于肾上腺皮质。本申请的第三个目的是确定 骨钙素对肾上腺发育/功能影响的时间过程， 研究母体骨钙素如何影响后代的这一过程。我们会用老鼠的基因， 分子和生物化学测定来研究骨和骨组织之间的相互作用的分子基础。 肾上腺通过骨钙素调节肾上腺类固醇激素的产生。该应用程序将 通过以下方法，我们对脊椎动物肾上腺发育和生理学有了更深入的了解 描述了一种肾上腺发育和类固醇生成的新调节，其来源于 母亲和生物相关，因为它的缺失可能是致命的。

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.