How do glucocorticoids inhibit prostaglandin production

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Because glucocorticosteroids reduce inflammation, possibly through inhibition of arachidonic acid release, we examined the influence of dexamethasone on PG formation in cultures of human endothelial cells. Binding of [3H]dexamethasone by intact cells was competed by unlabeled steroids and was half-maximal at 1. A cytosolic fraction complexed with [3H]dexamethasone and migrated on sucrose density gradient centrifugation with a sedimentation coefficient of 8S.

Studies indicate that several polyglutamine diseases, including HD, are caused by multiple C-A-G repeats within a unique gene A section of DNA that codes for a specific functional product, such as a protein. The altered genes result in the production of altered proteins that cause selective nerve cell death within the nervous system.

For example, polyglutamine expansion within the androgen receptor AR protein results in SBMA, a disease associated with selective death of motor nerve cells. Studies indicate that the nerve cell death associated with these polyglutamine diseases may be linked to the formation of neuronal aggregates of the altered proteins.

These altered proteins have been found to form aggregates called neuronal inclusions NIs in the nucleus of the nerve cell. For more on NIs, click here. Some studies have shown that reducing aggregate formation could improve conditions in animal models of the polyglutamine diseases.

The researchers in the current study attempted to discover ways on how these aggregations can be reduced. Based on the role of GRs as regulators of transcription , the researchers wondered whether they may have any role in the aggregation of polyglutamine proteins. The researchers found that the addition of dexamethasone to human kidney cells and mouse nerve cells expressing HD reduced the aggregation of the altered huntingtin protein. The results of the study indicate that aggregation of expanded polyglutamine proteins are regulated within the cell.

The aggregation process can be manipulated through glucocorticoid-controlled gene expression. The researchers believe that the glucocorticoid-GR complex acts as a transcriptional regulator: in the nucleus , the complex binds to sites that can control and modulate the expression of nearby genes. It is possible that the transcriptional changes induced by the complex may result in the production of proteins that could inhibit polyglutamine aggregation. What proteins are produced is still currently unknown.

More studies need to be done to identify the genes and proteins involved in the pathways that determine polyglutamine aggregations and nerve cell dysfunction. However, the results of this study raise the possibility that glucocorticoids could reduce polyglutamine aggregations. By reducing these aggregations, glucocorticoids could play essential roles in delaying or inhibiting the progression of diseases such as HD, SBMA, and possibly other polyglutamine diseases as well. Our goal is to survey the rapidly growing scientific literature on HD and to present this information in a web source.

We emphasize that we are neither medical professionals, nor are we affiliated with the researchers and laboratories mentioned on our pages. The information we present is intended for educational purposes only and should not be construed as offering diagnoses or recommendations.

We operate as a not-for-profit public service organization, and our funding is entirely from private sources. Blog Section Drug Summary: Glucocorticoids are powerful anti-inflammatory compounds that have the ability to inhibit all stages of the inflammatory response. What are glucocorticoids? The adrenal glands are organs located immediately above our kidneys AD.

Abbreviation for Alzheimer's disease, a neurodegenerative disease that causes progressive memory loss and severe dementia in advanced cases. Usually abbreviated as DNA, which is the 'instruction manual' that directs the growth and development of the cells and body. A section of DNA that codes for a specific functional product, such as a protein. Flower, R. The importance of phospholipase A 2 in prostaglandin biosynthesis.

Gryglewski, R. Steroid hormones, anti-inflammatory steroids and prostaglandin. Danon, A. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Di Rosa, A. Mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leukocytes.

Anti-inflammatory steroids induce biosynthesis of a phospholipase A 2 inhibitor which prevents prostaglandin generation. Russo-Marie, F.