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Sex Differences in Renal Ammonia Metabolism

肾脏氨代谢的性别差异

基本信息

批准号：
10552695
负责人：
AUTUMN N HARRIS
金额：
$ 15.85万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10552695
关键词：
Acceleration Acids Advisory Committees Affect Ammonia Androgen Receptor Animal Model Area Cardiovascular system Caring Chromosome 3 Chromosomes Chronic Kidney Failure Collaborations Cre-LoxP Data Development Diagnostic tests Disease Disease model Duct (organ) structure Eating Enzymes Equipment Estrogen Receptor alpha Estrogen Receptors Estrogens Evaluation Excretory function Female Florida Four Core Genotypes Functional disorder Funding Future Generations Goals Gonadal Steroid Hormones Grant Health Homeostasis Hormones Human Immunologics Institution Intestines Investigation K-Series Research Career Programs Kidney Laboratories Maintenance Male Castration Manuscripts Mediating Medical center Medicine Mentors Metabolic acidosis Metabolism Modeling Mus Musculoskeletal Nephrology Neurologic Orchiectomy Ovariectomy Ovary Performance Persons Phenotype Physiological Physiology Ploidies Postdoctoral Fellow Prevalence Process Production Progesterone Proteins Proximal Kidney Tubules Publishing Regulation Research Research Design Research Personnel Resources Role Sex Chromosomes Sex Differences Statistical Methods Stimulus Structure System Techniques Testing Testis Testosterone Therapeutic Training Translating Treatment outcome United States National Institutes of Health Universities Writing Y Chromosome base biological sex body system college density gonad development human disease improved kidney cortex laboratory experience male mortality multidisciplinary patient oriented programs protein expression receptor receptor expression reproductive function respiratory response sex sexual dimorphism sry Genes steroid hormone receptor supportive environment

项目摘要

Project Summary Males and females differ in their basic physiology and pathophysiology in essentially all physiological systems. These biological sex differences can lead to differences in disease prevalence, progression rates and treatment outcomes. Understanding these differences can serve to identify new disease mechanisms and/or new and improved therapeutic opportunities. Thus, there is an immense need for additional research into the area of sex differences in both animal models and people. Acid-base homeostasis is of critical importance for maintaining normal health and renal ammonia metabolism has a major role in the maintenance of acid-base homeostasis. I have shown there are significant sex differences in basal ammonia excretion that result from sex differences in the expression of multiple important proteins involved in ammonia metabolism and transport. Furthermore, I have shown that there are significant structural differences between the female and male kidney. Hence, the overall objective of this proposal is to determine the underlying mechanisms of these sex differences in renal ammonia metabolism and to determine the role of these sex differences in physiological relevant disease models. This objective will be evaluated via the following specific aims: 1) determine the role of sex steroid hormones in the regulation of renal ammonia metabolism using a gonadectomy and hormone replacement model; 2) determine the role of sex steroid hormone receptors in the development of sex-dependent differences in ammonia metabolism through the use of kidney-specific AR and ERα deletion; 3) determine the role of sex chromosomes in the regulation of renal ammonia metabolism using the four core genotype model; and, 4) determine the effect of sex on the renal response to conditions of altered ammonia metabolism such as metabolic acidosis. Autumn Harris, DVM, DACVIM (SAIM), is an NIH T32-funded post-doctoral research fellow at the University of Florida College of Medicine. This career development award will provide Dr. Harris with the additional training needed to achieve her goal of becoming an independent investigator, which includes training in the areas of 1) study design and implementation, 2) performance, interpretation, and evaluation of various laboratory techniques and diagnostic tests, 3) statistical methods and interpretation, 4) collaboration with a multidisciplinary and multi-institutional team, 5) grant and manuscript writing. Dr. Harris has developed a comprehensive program including didactic training, practical and laboratory experience, and a strong mentoring and advisory team. The University of Florida College of Medicine will provide a collegial and supportive environment with the equipment, laboratory space, and resources necessary to complete the research and training. At the culmination of this proposal, Dr. Harris will be poised to achieve independence as a researcher with continuing investigation in the field of nephrology and sex differences.

项目总结