If you've ever wondered why women are susceptible to bouts of anxiety, sadness and irritability as she nears her monthly period, researchers from the National Institutes of Health may have an answer for you.
In a study published in the journal Molecular Psychiatry, NIH researchers detailed their discovery of the molecular mechanisms possibly underlying premenstrual dysphoric disorder (PMDD) and its less severe sibling, premenstrual syndrome (PMS). Between 2 and 5 percent of women within reproductive age are affected by PMDD while PMS is more common.
Having uncovered dysregulated expression within a suspected gene complex, Peter Schmidt, M.D. and colleagues said their discovery adds to proof that PMDD is a condition related to cellular response issues with progesterone and estrogen, adding that learning more regarding the gene complex will help in improving treatment for prevalent mood disorders related to reproductive endocrines.
"This is a big moment for women's health, because it establishes that women with PMDD have an intrinsic difference in their molecular apparatus for response to sex hormones," said study author David Goldman, M.D.
Yes, it's not just about emotional behaviors that women should be able to control voluntarily.
PMDD Research
Toward the end of the 1990s, the National Institute of Mental Health (NIMH) of the NIH was able to show that women who routinely experience symptoms of mood disorders just before their periods had abnormal sensitivity to the usual sex hormone changes, even when these hormones are at normal levels.
Researchers have been unable to explain why but experiments where progesterone and estrogen were turned off in women with PMDD demonstrated that doing so eliminated symptoms. When the hormones were activated again and symptoms reemerged, this is when the researchers were able to confirm that there was a biological basis for behavioral sensitivity related to hormones, which may show up in differences found in cells at the molecular level..
Building upon earlier works, researchers for the current study explored genetic control over gene expression in the white blood cell lines of a control group and women with PMDD. As these cells express a lot of the genes that are expressed as well in brain cells, the researchers considered that they might gain a window into differences in sex hormone molecular responses that are generically influenced.
After analyzing gene transcriptions in cultured cell lines, the researchers observed an expansive gene complex where cells from women with PMDD exhibited gene expression that stood out in comparison to those of the control group.
This gene complex is called Extra Sex Combs/Enhancer of Zeste – ESC/E(Z) – and it is tasked with regulating gene-to-protein transcription in response to environmental factors, such as stressors and sex hormones.
Abnormal Gene Expression In Women With PMDD
In women with PMDD, over half of the genes belonging to ESC/E(Z) were over-expressed but protein expression related to four crucial genes were also low. Additionally, the researchers saw that women with PMDD had reduced estrogen expression within their cell lines while there was an increase in progesterone expression in some of the genes in the control group. This pointed to dysregulated cell response to hormones in those with PMDD.
According to Schmidt, they now have cellular evidence for abnormal cell signaling in women with PMDD for the first time. For their next step, the researchers will be following up on leads to better observe how the gene complex ESC/E(Z) affects the brain.
