Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Gene Linked to Excess Male Hormones in Female Infertility Disorder

Published: Thursday, April 17, 2014
Last Updated: Thursday, April 17, 2014
Bookmark and Share
Discovery by NIH-supported researchers may lead to diagnostic test, treatment.

A variant in a gene active in cells of the ovary may lead to the overproduction of androgens - male hormones similar to testosterone - occurring in women with polycystic ovary syndrome (PCOS) (http://www.nichd.nih.gov/health/topics/PCOS/Pages/default.aspx), according to scientists funded by the National Institutes of Health. The discovery may provide information to develop a test to diagnose women at risk for PCOS and also for the development of a treatment for the condition.

In addition to high levels of androgens, symptoms of PCOS include irregular menstrual cycles, infertility, and insulin resistance (difficulty using insulin.) The condition affects approximately 5 to 7 percent of women of reproductive age and increases the risk for heart disease, high blood pressure and type 2 diabetes. In PCOS, higher levels of androgens may also cause excess facial and body hair, as well as severe acne.

"PCOS is a major cause of female infertility and is associated with other serious health problems," said Louis V. De Paolo, chief of the Fertility and Infertility Research Branch of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, which funded the study. "In identifying this gene, the study authors have uncovered a promising new lead in the long search for more effective ways to diagnose and treat the condition, and perhaps, to one day prevent it from even occurring."

The study was published online in the Proceedings of the National Academy of Sciences. The study's primary author was Jan M. McAllister, Ph.D, professor of pathology, obstetrics and gynecology, and cellular and molecular physiology in the Penn State College of Medicine, Hershey, Pa.

The researchers narrowed their search to the gene called DENND1A, which contains the information needed to make a protein. This protein is made in theca cells, which line the inner surface of ovarian follicles, the temporary, sphere-like structures which ultimately break open and give rise to the egg each month.

In women with PCOS, the follicles fail to mature normally. Instead of rupturing during the monthly cycle to release the egg, the follicles accumulate and form numerous cyst-like structures. Previous studies have shown that in PCOS, theca cells are the source of the high levels of androgens found in women with the condition.

PCOS appears to run in families, but no genes have been definitively linked to the disorder. Researchers believe that PCOS probably results from the interaction of several genes, and perhaps to interactions between certain genes and the environment.

Previously, researchers conducting genome-wide scans (searches of all of a person's genes) of women in China identified several candidate genes in locations on chromosomes that were associated with the disease. One of these locations harbored the gene for DENND1A. Researchers conducting genome-wide scans of people of Asian and European descent also confirmed the gene's association with PCOS.

For the current study, Dr. McAllister and her colleagues grew theca cells from women with PCOS in laboratory dishes. Compared to theca cells from women without PCOS, theca cells taken from women with PCOS produced high levels of a variant form of DENND1A, DENNDA1A.V2. V2 indicates variant 2, to distinguish it from the more commonly seen form of the protein, known as DENND1A.V1.

The researchers next conducted a battery of experiments on the cells to determine what role DENND1A.V2 might play in PCOS. They began by manipulating the theca cells from women who did not have PCOS to produce high levels of DENND1A.V2. The theca cells, which previously functioned normally, began producing elevated levels of androgens. Similarly, when the researchers blocked the function of DENND1A.V2 in theca cells from women with PCOS, androgen levels in those cells dropped sharply, as did to the activity of other genes that make androgen and the levels of messenger RNA needed to produce androgens. The study authors noted that DENND1A.V2 is also found in other cells that make androgens, including cells in the testes, as well as in a type of cancer cell occurring in the adrenal glands.

The cells from women with PCOS also contained higher levels of the messenger RNA for DENND1A.V2. Messenger RNA converts the information contained within DNA into a protein.

In addition, the researchers found that the messenger RNA for DENND1A.V2 protein was higher in urine samples from PCOS patients than in urine samples of women in the control group.

"PCOS is often difficult to diagnose, especially in adolescents," Dr. McAllister said. "The fact that DENND1A.V2 is present in urine opens up the possibility that it might provide the basis for a test to screen for PCOS."


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
Mystery of the Tubulin Code Unravelled
NIH study provides a glimpse into the code that controls variety of cell functions.
Wednesday, May 13, 2015
Mouse Study Reveals Potential Clue to Extra Fingers or Toes
NIH-funded study finds that gene appears to regulate protein signals inside the cell.
Tuesday, December 02, 2014
NIH Grant for Texas Biomed to Perform Mass Spec-Based Studies into Heart Disease
Institute awarded $2.7M grant from the NIH to fund innovative approaches to genetics research for the development of new therapies for heart disease and other conditions.
Wednesday, August 20, 2014
GTEx Project to Expand Functional Studies of Genomic Variation
Larger set of human tissues to be analyzed to contribute to a database and tissue bank that researchers can use to study how genomic variants influence gene activity.
Wednesday, August 06, 2014
Subcellular Imaging Visualizes Structures of Brain Receptors
The advance opens a new window to study protein interactions in cell membranes in exquisite detail.
Tuesday, August 05, 2014
NIH Funds $24M into Alzheimer’s Disease Genome Research
Scientists will analyze genome sequence data to identify gene risk, protective factors.
Tuesday, July 08, 2014
Muscle Weakness Seen in Alcoholism Linked to Mitochondrial Repair Issues
Scientists found evidence that chronic heavy alcohol use affects a gene involved in mitochondrial repair and muscle regeneration.
Tuesday, April 22, 2014
Unexpected Protein Partnership has Implications for Cancer Treatment
Scientists have identified a macrophage that works together in response to cancer drugs to increase inflammation in a way that may alter tumor growth.
Tuesday, April 15, 2014
Too Much Protein May Kill Brain Cells As Parkinson’s Progresses
NIH-funded study on key Parkinson’s gene finds a possible new target for monitoring the disease.
Friday, April 11, 2014
Underlying Genetics and Marker For Stroke Discovered
NIH-funded findings point to new potential strategies for disease prevention, treatment.
Friday, March 21, 2014
Speeding Validation of Disease Targets
NIH, industry and non-profits join forces to develop new treatments earlier, beginning with Alzheimer’s, type 2 diabetes, and autoimmune disorders.
Tuesday, February 04, 2014
Study Breaks Blood-Brain Barriers to Understanding Alzheimer’s
NIH-funded study suggests brain blood vessel cells may be therapeutic targets for Alzheimer’s disease.
Friday, December 13, 2013
Epigenetic Clock Marks Age of Human Tissues and Cells
The age of many human tissues and cells is reflected in chemical changes to DNA. The finding provides insights for cancer, aging, and stem cell research.
Tuesday, November 05, 2013
Scientific News
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Study Finds Non-Genetic Cancer Mechanism
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Rice Disease-Resistance Discovery Closes the Loop for Scientific Integrity
Researchers reveal how disease resistant rice detects and responds to bacterial infections.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!