Transcription regulation of NRF1 on StAR reduces testosterone synthesis in hypoxemic murine.

08:00 EDT 24th April 2019 | BioPortfolio

Summary of "Transcription regulation of NRF1 on StAR reduces testosterone synthesis in hypoxemic murine."

Male chronic obstructive pulmonary disease (COPD) and sleep apnea patients are associated with serum testosterone level decline because of hypoxemia, resulting in male sexual dysfunction and lower reproductive capacity. Although testosterone replacement therapy used in clinic achieves good results, the side effects indicates that understanding the mechanism followed with targeted treatments are more meaningful. The known mechanism of Hypoxia-inducible factor-1 (HIF-1) mediated steroidogenic acute regulatory protein (StAR) repression did not well explain the reason of hypoxia induced testosterone decline. Our primary results indicated Nuclear respiratory factor 1(NRF1) might be participate in StAR transcription regulation. The study aims to identify the mechanism of the regulation of StAR by NRF1, providing an explanation for the decrease of testosterone induced by hypoxemia. Testosterone level and StAR were determined in COPD model rats, sleep apnea model mice and hypoxia rats (10%O). Results indicated NRF1, StAR and testosterone decreased in testis and ovary and increased in adrenal. Regulation of NRF1 expression under normoxia or hypoxia induced synchronous changes of both StAR and testosterone, indicating the decrease of NRF1 induced StAR repression in hypoxemia were the main cause of serum testosterone decline. The results were confirmed by dual-luciferase reporter assays, regulation of NRF1 synchronously altered the transcriptional activity of StAR. By ChIP, EMSA supershift, NRF1 was found to bind to the Star promoter region. Mutation assays identified two NRF1-binding sites on mouse Star promoter. These findings indicated that NRF1 positivly regulated Star transcription through directly binding to the Star promoter at -1445/-1422 and -44/-19.


Journal Details

This article was published in the following journal.

Name: The Journal of steroid biochemistry and molecular biology
ISSN: 1879-1220


DeepDyve research library

PubMed Articles [14085 Associated PubMed Articles listed on BioPortfolio]

Small molecule stimulators of NRF1 transcriptional activity.

The transcription factor NRF1 maintains proteostasis and promotes cellular resilience by stimulating the transcription of proteasomal subunits and a host of protective enzymes. Although NRF1 activatio...

Protective effects of l-arginine against testosterone synthesis decreased by T-2 toxin in mouse Leydig cells.

The testosterone levels decreased by T-2 toxin in mouse Leydig cells were reported previously. It is not known, however, whether l-arginine improves the situation and what's the mechanism. Leydig cell...

Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH.

Studies in vivo have suggested the involvement of CREB-regulated transcription coactivator (CRTC)2 on ACTH-induced transcription of the key steroidogenic protein, Steroidogenic Acute Regulatory (StAR)...

MiR-1197-3p regulates testosterone secretion in goat Leydig cells via targeting PPARGC1A.

As a fundamental regulator of mitochondrial function, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors tha...

Bioinformatics analysis and transcription regulation of TORC1 gene through transcription factors NRF1 and Smad3 in bovine preadipocytes.

Intramuscular fat is the an important factor that defines meat quality; however, enhancing its deposition without increasing the other three adipose depots (subcutaneous, visceral, and intermuscular f...

Clinical Trials [3657 Associated Clinical Trials listed on BioPortfolio]

Randomized Study of Testosterone and Progressive Resistance Exercise in Men With Burn Injury

OBJECTIVES: I. Determine whether testosterone normalization ameliorates muscle protein hypercatabolism by increasing net protein synthesis in men with burn injury. II. Determine whether t...

Systemic Hormones and Muscle Protein Synthesis

This study evaluates the effect of increase in testosterone levels in older males and the effects of decrease in testosterone levels in young males on muscle protein synthesis.

Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

Naturally occurring opiates (endorphins) decrease testosterone levels by inhibiting the synthesis of gonadotropin releasing hormone (GnRH) and also inhibiting testosterone synthesis by the...

Subcutaneous vs. Intramuscular Testosterone

In this randomized, cross‐over study 20 subjects who are undergoing testosterone (T) therapy for the treatment of T deficiency will receive both subcutaneous testosterone therapy and int...

Testosterone Therapy and Bone Quality in Men With Diabetes and Hypogonadism

Low testosterone and diabetes mellitus are each associated with increased risk for fractures. Men with diabetes mellitus are commonly found to have low testosterone as well. Testosterone h...

Medical and Biotech [MESH] Definitions

A small maf protein that forms dimers with NRF1 protein; NRF2 PROTEIN; and P45 NF-E2 PROTEIN. MafF complexes bind Maf recognition elements to regulate tissue-specific GENETIC TRANSCRIPTION.

Steroidal compounds related to TESTOSTERONE, the major mammalian male sex hormone. Testosterone congeners include important testosterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with androgenic activities.

Basic helix-loop-helix (bHLH) domain-containing proteins that play important roles in CIRCADIAN RHYTHM regulation. They combine with CLOCK PROTEINS to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation.

An RNA polymerase II transcriptional inhibitor. This compound terminates transcription prematurely by selective inhibition of RNA synthesis. It is used in research to study underlying mechanisms of cellular regulation.

A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.

Quick Search

DeepDyve research library

Relevant Topics

Diabetes Diabetes Endocrine Disorders Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several g...

COPD (chronic obstructive pulmonary disease)
COPD (chronic obstructive pulmonary disease) is used for a number of conditions including chronic bronchitis and emphysema, which all  lead to the airways in the lungs becoming damaged and thus narrower,  making inhalation and exhalation harder...

Searches Linking to this Article