Hypertension after menopause: not only sex hormones, but also sex chromosomes
The generally accepted opinion that sex hormones play a major role in the development of hypertension in women after menopause has been challenged by Georgetown University scientists working under the leadership of Kathryn Sandberg. In the article "Sex Chromosome Effects Unmasked in Angiotensin II–Induced Hypertension", published on March 15 in the preliminary on-line version of the journal Hypertension, the authors showed that in some cases, the mechanisms that increase blood pressure are triggered not by a change in hormonal status, but by the female sex chromosomes themselves.
In their work, the researchers used genetically modified mice whose sex was determined by manipulations performed on the Sry gene. This gene, usually localized on the Y chromosome, is necessary for the formation of seminal glands and, accordingly, the development of the male organism. In the mice used in the experiment with the male genotype XY, the Sry gene was removed from the Y chromosome, which led to the formation of a female organism. Conversely, mice with the female genotype XX had a male gender due to the Sry gene embedded in the 22nd somatic chromosome of their genome.
The use of such animals makes it possible to identify the influence of sex chromosomes on certain signs. For example, the only difference between females having XX and XY genotypes, whose organisms developed in the uterus under the same hormonal background, is a set of sex chromosomes. The same can be said about males with XX and XY genotypes. Therefore, any difference between such pairs of females or males is due solely to a set of sex chromosomes.
The authors found that, regardless of gender, mice with the XX genotype have a pronounced predisposition to the development of hypertension. This means that the X chromosome itself contains some information that affects the level of blood pressure regardless of the hormonal background, the role of which in the development of hypertension is a proven fact.
Dr. Sandberg notes that scientists have already identified the influence of sex chromosomes on the functioning of the immune system and certain regions of the brain, but so far no one has studied their role in the cardiovascular system.
She also lists three possible explanations for the phenomenon discovered by the authors. One of them is a feature of the expression of genes localized on the X chromosomes. In each cell having the XX genotype, only one of the X chromosomes inherited from the parents is expressed. The second X chromosome, as a rule, is in an inactivated state. However, it is known that some genes of the "silent" X chromosome avoid inactivation in both female and male cells with the XX genotype. Perhaps one of these genes or their complex influences the functioning of the cardiovascular system.
Another possible explanation is the conflict that occurs between the cells of the body expressing different X chromosomes. Part of the body's cells with the XX genotype express the maternal X chromosome, and the other part expresses the paternal one. The neighborhood of such cells can trigger an immune response, the consequence of the development of which is an increase in blood pressure.
According to the last of the three hypotheses proposed by the authors, the Y chromosome may contain a gene or genes that prevent the development of hypertension. Therefore, women who have reached menopause and, accordingly, deprived of the protective effect of estrogen, in the absence of Y-chromosome genes, hypertension can develop.
The authors believe that finding out the exact mechanism underlying the influence of sex chromosomes on blood pressure regulation will allow the development of new effective methods for the treatment of hypertension in elderly women.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Female Sex Chromosomes, Not Just Hormones, Help Regulate Blood Pressure.
17.03.2010