Navigation Links
Lack of key enzyme associated with development of rare tumor

Researchers at the National Institutes of Health have discovered that a rare tumor of the adrenal glands appears to result from a genetic deficiency of an important enzyme. The enzyme is one of a class of enzymes involved in halting a cell's response to hormones and appears to stop cells from dividing.

The study, published in Nature Genetics, was conducted by researchers in NIH's National Institute of Child Health and Human Development. The NIH group collaborated with scientists from the Mayo Clinic, the Cochin Institute in Paris, the University of Paris, Ohio State University in Columbus, and the Universitaire Vaudois in Lausanne, Switzerland, in collecting samples from patients with rare adrenal disorders. Scientists from Sapio Sciences in York, Pennsylvania, assisted in the analysis of the data.

In conducting the study, the researchers used gene arrays to analyze the DNA of patients with a rare tumor of the adrenal glands, known as micronodular adrenocortical hyperplasia, explained the study's senior author, Constantine Stratakis, M.D., D(Med)Sc, Chief of NICHD's Section on Endocrinology and Genetics. The researchers also used the technology to analyze samples of the patients' tumors.

The researchers found four patients who had mutant copies of a gene that contains the information for Phosphodiesterase 11A (PDE11A). Phosphodiesterases are a family of enzymes involved in "switching off" a cell's response to hormones, Dr. Stratakis explained.

For a hormone to affect the cell, it must first bind to a molecule, or receptor, on the cell's surface, analogous to how a key fits into a lock. This action triggers the cell to produce substances known as cyclic nucleotides. These function as "second messengers," often stimulating the cell to begin an activity. In the case of adrenal cells, cyclic nucleotides, such as cyclic AMP and cyclic GMP, may stimulate cell growth or other activities. Once the activity has ended, phosphodiesterases degrade the cyclic nucleotides, thereby halting the cell's response to the hormone.

In the study, the patients' tumors were made up of cells that were deficient in the enzyme PDE11A. This enzyme halts cyclic nucleotide production in adrenal cells as well as in other kinds of cells in the body. Because they lacked PDE11A, the patients' adrenal cells had higher levels of cyclic nucleotides. The researchers believe that these higher cyclic nucleotide levels led to the formation of tumors.

The gene for PDE11A contains the information needed to make 4 slightly different forms of the enzyme. The form of the enzyme that was mutated in the patients who took part in the study was found in large amounts in normal adrenal glands and in even larger amounts in normal prostate glands, Dr. Stratakis added. Other forms of PDE11A are found in several other tissues, including the testes, skeletal muscle, and the heart.

Dr. Stratakis noted that although the evidence associating the mutation in the gene for PDE11A to the development of adrenal tumors was very strong, the study was not capable of proving that the mutation actually caused the tumors.

In their article, the researchers wrote that drugs used to treat erectile dysfunction interfere with the functioning of PDE11A. The researchers noted that PDE11A "is partially inhibited" by the drug tadalafil and "weakly" inhibited by sildenafil. They added that there are no reports in the medical literature of malfunctioning adrenal glands or increased adrenal cell growth in users of these drugs.

"However, detailed clinical studies addressing this potential complication are currently lacking," they wrote.

Dr. Stratakis and his colleagues are currently planning studies to determine if differences in the gene for PDE11A might influence an individual's cancer risk.


'"/>

Source:NIH/National Institute of Child Health and Human Development


Related biology news :

1. Lack of enzyme turns fat cells into fat burners
2. Scientists find missing enzyme for tuberculosis iron scavenging pathway
3. Researchers report new pro-inflammatory role for anti-inflammatory enzyme
4. Purdue researchers use enzyme to clip DNA wires
5. Scientists take aim at virulent bacteria by decoding machinery of key control enzyme
6. VCU Massey Cancer Center study shows enzyme linked to spread of breast cancer cells
7. Targeting a key enzyme with gene therapy reversed course of Alzheimers disease in mouse models
8. UCLA researchers identify key enzyme linked to childhood blindness
9. K-State professors discover enzyme responsible for creation of a beetles hard shell
10. Smoking damages key regulatory enzyme in the lung
11. New discovery: If it werent for this enzyme, decomposing pesticide would take millennia
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/30/2017)... June 30, 2017 Today, American Trucking ... supplier of face and eye tracking software, became ... provider program. "Artificial intelligence and ... to monitor a driver,s attentiveness levels while on ... able to detect fatigue and prevent potential accidents, ...
(Date:6/14/2017)... , June 15, 2017  IBM (NYSE: IBM ) is ... tech event dedicated to developing collaboration between startups and global ... June 15-17. During the event, nine startups will showcase the ... in various industries. France ... international market, with a 30 percent increase in the number ...
(Date:5/16/2017)... May 16, 2017  Veratad Technologies, LLC ( www.veratad.com ... age and identity verification solutions, announced today they will ... 2017, May 15 thru May 17, 2017, in ... International Trade Center. Identity impacts the ... in today,s quickly evolving digital world, defining identity is ...
Breaking Biology News(10 mins):
(Date:8/21/2017)... ... August 21, 2017 , ... Finalists ... awards recognize medical centers that have implemented innovative products, services, and technology over ... protocols, competitive advantages, financial impact/value, and market need. The applicants with the top ...
(Date:8/21/2017)... (PRWEB) , ... August 21, 2017 , ... ... for two speakers for this two-part educational webinar, in which attendees will learn ... and associated protein factor composition. Along with an overview of the development and ...
(Date:8/18/2017)... Jose, CA (PRWEB) , ... August 18, 2017 ... ... advanced precision Lithography Equipment for the Semiconductor, MEMS, and Microfluidics Industries, announces the ... features and specifications found more often in automated production mask aligners. OAI has ...
(Date:8/16/2017)... PA (PRWEB) , ... August 16, 2017 , ... ... taking part in sessions at the ISPE Annual Meeting and Expo , to ... San Diego Marina. The event’s theme is “Driving innovation to advance patient therapies.” , ...
Breaking Biology Technology: