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

• 批准号: 10671698
• 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
• 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/10671698
• 关键词: ARHGEF5 gene; Ablation; Acute; Adrenal Cortex; Adrenal Glands; Adrenal Medulla; Adrenal gland hypofunction; Affect; Aldosterone; Anatomy; Area; Binding; Biochemical; Biological Assay; Biology; Birth; Brain; Catecholamines; Cells; Chronic; Circulation; Cognition; Corticosterone; Corticotropin; Development; Developmental Process; Electrolytes; Embryo; Endocrine Glands; Endocrinology; Epinephrine; Exhibits; Feedback; Genetic; Glucocorticoids; Goals; Growth; Heterozygote; Hippocampus; Homeostasis; Hormones; Hydrocortisone; In Vitro; Injections; Insulin; Mineralocorticoids; Molecular; 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; Topical application; 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; loss of function; mouse genetics; mouse model; novel; offspring; peptide hormone; postnatal; receptor; steroid hormone

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.

项目摘要 该应用的总体目标是提高我们对遗传和分子控制的理解 肾上腺稳态通过研究骨钙蛋白如何起源于孕妇骨架，影响肾上腺 发育期间和出生后后代的生长和类固醇发生。具体来说，我们打算1] 确定材料OCN对于适当的肾上腺发育和功能是必要的。我们还将2] 通过遗传和体内建立骨钙素有利于信号传导的肾上腺生长和类固醇生成 直接通过其接收器GPR158在肾上腺皮质中。此应用程序的第三目的是确定 精确的骨钙素对肾上腺发育/功能的影响的临时过程和 研究母体骨钙素在后代中如何影响这一过程。我们将使用小鼠遗传， 分子和生化测定法研究骨骼和 肾上腺通过骨钙素通过肾上腺素的产生调节。一起，这个应用程序将 显着提高了我们对骨脊椎动物中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，该调节起源于 母亲并且在生物学上是相关的，因为它的缺席可能是致命的。

项目成果

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

母体和胚胎来源的骨钙素协同作用，在后代中建立体内平衡。

• DOI: 10.1038/s44319-023-00031-3
• 发表时间: 2024
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: CorreaPintoJunior,Danilo;CanalDelgado,Isabella;Yang,Haiyang;Clemenceau,Alisson;Corvelo,André;Narzisi,Giuseppe;Musunuri,Rajeeva;MeyerBerger,Julian;Hendricks,LaurenE;Tokumura,Kazuya;Luo,Na;Li,Hongchao;Oury,Franck;Ducy,Patrici
• 通讯作者: Ducy,Patrici