Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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 2,500+ 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

NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Thursday, August 27, 2015
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Thursday, August 27, 2015
In Uveitis, Bacteria in Gut May Instruct Immune Cells to Attack the Eye
NIH scientists propose novel mechanism to explain autoimmune uveitis.
Wednesday, August 19, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Large Percentage of Youth with HIV May Lack Immunity to Measles, Mumps, Rubella
NIH study finds those vaccinated before starting modern HIV therapy may be at risk.
Tuesday, August 18, 2015
Cellular Factors that Shape the 3D Landscape of the Genome Identified
Researchers have identified 50 cellular factors required for the proper 3D positioning of genes by using novel large-scale imaging technology.
Tuesday, August 18, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
Newly Discovered Cells Restore Liver Damage in Mice Without Cancer Risk
The liver is unique among organs in its ability to regenerate after being damaged. Exactly how it repairs itself remained a mystery until recently, when researchers supported by the NIH discovered a type of cell in mice essential to the process
Monday, August 17, 2015
Study Finds Cutting Dietary Fat Reduces Body Fat More than Cutting Carbs
In a recent study, restricting dietary fat led to body fat loss at a rate 68 percent higher than cutting the same number of carbohydrate calories when adults with obesity ate strictly controlled diets.
Friday, August 14, 2015
Inappropriate Medical Food Use in Managing Patients with a Type of Metabolic Disorder
Researchers have proposed that there is a need for more rigorous clinical study of dietary management practices for patients with IEMs, including any associated long-term side effects, which may in turn result in the need to reformulate some medical foods.
Friday, August 14, 2015
PINK1 Protein Crucial for Removing Broken-Down Energy Reactors
NIH study suggests potential new pathway to target for treating ALS and other diseases.
Thursday, August 13, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Neurons’ Broken Machinery Piles Up in ALS
NIH scientists identify a transport defect in a model of familial ALS.
Thursday, August 13, 2015
Dr. Peter Kilmarx Appointed Deputy Director of Fogarty International Center
An expert in infectious disease research and HIV/AIDS prevention.
Wednesday, August 12, 2015
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Less May Be More in Slowing Cholera Epidemics
Mathematical model shows more cases may be prevented and more lives saved when using one dose of cholera vaccine instead of recommended two doses.
Investigating the Vape
Expert independent review concludes that e-cigarettes have potential to help smokers quit.
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Researchers Discover Synthesis of a New Nanomaterial
Interdisciplinary team creates biocomposite for first time using physiological conditions.
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Flu Remedies Help Combat E. coli Bacteria
Physiologists from the University of Zurich have now discovered why the intestinal bacterium Escherichia coli (E. coli) multiplies heavily and has an inflammatory effect.
Marijuana Genome Unraveled
A study by Canadian researchers is providing a clearer picture of the evolutionary history and genetic organization of cannabis, a step that could have agricultural, medical and legal implications for this valuable crop.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!