A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling.

Abstract

Progesterone is primarily a pregnancy-related hormone, produced in substantial quantities after ovulation and during gestation. Traditionally known to function via nuclear receptors for transcriptional regulation, there is also evidence of nonnuclear action. A previously identified mitochondrial progesterone receptor (PR-M) increases cellular respiration in cell models. In these studies, we demonstrated that expression of PR-M in rat H9c2 cardiomyocytes resulted in a ligand-dependent increase in oxidative cellular respiration and beta-oxidation. Cardiac expression in a TET-On transgenic mouse resulted in gene expression of myofibril proteins for remodeling and proteins involved in oxidative phosphorylation and fatty acid metabolism. In a model of increased afterload from constant transverse aortic constriction, mice expressing PR-M showed a ligand-dependent preservation of cardiac function. From these observations, we propose that PR-M is responsible for progesterone-induced increases in cellular energy production and cardiac remodeling to meet the physiological demands of pregnancy.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1210/js.2018-00219

Publication Info

Dai, Qunsheng, Creighton E Likes, Anthony L Luz, Lan Mao, Jason S Yeh, Zhengzheng Wei, Maragatha Kuchibhatla, Olga R Ilkayeva, et al. (2019). A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling. Journal of the Endocrine Society, 3(2). pp. 446–467. 10.1210/js.2018-00219 Retrieved from https://hdl.handle.net/10161/18107.

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Scholars@Duke

Lan Mao

Assistant Professor Emeritus in Medicine

I. Research:
As the director of mouse physiology laboratory, in charge for the all events related with Dr. Howard Rockman's molecular biology laboratory studies needs.
Participate in research in rodents model:
Perform surgery and serve as co-investigator in studies on transgenic mice with heart failure. Develop models of hypertrophy in small animal using micro-surgical techniques (aortic constriction, left ventricular infarction and abdominal aortocaval fistula) and perform a variety physiological studies, obtain and analysis data on hemodynamic study and prepare tissue specimens for father molecular biological study.
Develop and apply surgical techniques for in vivo myocardial function study on small animal, such as, using new developed devices study in vivo mice cardiac function (pressure-volume lop), instrumented mice for conscious blood pressure measure or administration of medicine---carotid artery or gull duck catheterization, and conscious mice echocardiography.
Develop techniques for micro-injection of proteins and vectors in to mouse left ventricle, coronary artery and portal vein.


II. Teaching
10% of time allocated/spent---
Train postdoctoral fellows, visiting scientists and students from all over the world in laboratory procedure involving, including endotracheal intubations, cardiac catheterization, coronary occlusion and intrathoracic/intra-abdominal surgical procedures.
Teach methods of data recording and analysis using laboratory equipment and computer programs, echocardiography apply and measurement.


III. Consultant
Consult and teach microsurgical techniques related on small animals such as, rabbits, rat, hamsters and mice, like mice heart-lung transplantation, portal vein injection and mini-pump implant.
Co-laboratory with large range of Universities and Research Institutes from United States an other countries.

Kuchibhatla

Maragatha Kuchibhatla

Professor of Biostatistics & Bioinformatics

Statistical research methodology, analysis of repeated measurements, latent growth curve models, latent class growth models, classification and regression trees,
designing clinical trials, designing clinical trials in psychiatry -- both treatment and non-treatment
trials in various comorbid populations.

Ilkayeva

Olga Ilkayeva

Assistant Professor in Medicine

Olga Ilkayeva, Ph.D., is the Director of the Metabolomics Core Laboratory at Duke Molecular Physiology Institute. She received her Ph.D. training in Cell Regulation from UT Southwestern Medical Center at Dallas, TX. Her postdoctoral research in the laboratory of Dr. Chris Newgard at Duke University Medical Center focused on lipid metabolism and regulation of insulin secretion. As a research scientist at the Stedman Nutrition and Metabolism Center, Dr. Ilkayeva expanded her studies to include the development of targeted mass spectrometry analyses. Currently, she works on developing and validating quantitative mass spectrometry methods used for metabolic profiling of various biological models with emphasis on diabetes, obesity, cardiovascular disease, and the role of gut microbiome in both health and disease.

Koves

Timothy Robert Koves

Associate Professor in Medicine

My research is focused on 1) understanding metabolic perturbations that occur in subpopulations of skeletal muscle mitochondria in response to a chronic high lipid environment, 2) identifying specific metabolites of lipid-induced mitochondrial stress that contribute to skeletal muscle insulin resistance and type II diabetes, and 3) understanding how mitochondrial adaptations in response to exercise confer protection against lipid-induced mitochondrial dysfunction.

Price

Thomas Michael Price

Professor Emeritus of Obstetrics and Gynecology

Dr. Price is involved in both clinical and basic science research. The main focus of the basic science molecular endocrinology laboratory is the study of novel sex steroid receptors. Currently, the work focuses on a novel progesterone receptor that localizes to the mitochondrion. Studies including RNAi in cell models and creation of transgenic mice are ongoing to discover the function of this receptor. The overall hypothesis is that progesterone modulates mitochondrial activity to meet the increased cellular energy demands of pregnancy via this receptor.
Dr. Price also participates in clinical research endeavors. These projects are constantly changing and focus on many aspects of reproductive endocrinology including ovarian preservation during chemotherapy, treatments for menorrhagia, endometriosis, leiomyomata and infertility.


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