Glucocorticoid Plays Key Role In Skin Abnormalities Induced By Psychological Stress

The study, "Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function," was carried out by Eung-Ho Choi, Marianne Demerjian, Debra Crumrine, Barbara E. Brown, Theodora Mauro, Peter M. Elias and Kenneth R. Feingold of the Veterans Affairs Medical Center, San Francisco and the University of California at San Francisco. Choi is also associated with Yonsei University Wonju College of Medicine, Wonju, Korea. The American Physiological Society published the study.

Previous research has shown that psychological stress increases glucocorticoid production. In addition, it is well recognized that psychological stress adversely affects many skin disorders, including psoriasis and atopic dermatitis.

"In this study, we showed that the increase in glucocorticoids induced by psychological stress induces abnormalities in skin structure and function, which could exacerbate skin diseases," Feingold explained. This provides a link for understanding how psychological stress can adversely affect skin disorders. Blocking the production or action of glucocorticoids prevented the skin abnormalities induced by psychological stress.

Skin protects

The skin is the body's largest organ and plays a crucial role in providing a barrier between the environment and the internal organs. It protects us from harmful microorganisms, ultraviolet light, toxic chemicals, and more. However, its most important function is providing a permeability barrier that prevents us from drying out. We are approximately 65 percent water and we are able to survive and function in dry environments because the skin forms a permeability barrier that prevents the loss of water.

The permeability barrier is located in the outermost layer of the epidermis, the stratum corneum. The stratum corneum is composed of dead cells surrounded by lipid membranes which mediate the permeability barrier. The stratum corneum layer continuously sloughs off, and therefore must be regenerated. The epidermal cells in the lower epidermis are continuously proliferating to provide new cells, which then differentiate, and ultimately die, to form the stratum corneum.

Previous studies have shown that psychological stress disturbs this elegantly balanced system by decreasing epidermal cell proliferation and inhibiting differentiation. Additionally, permeability barrier function is impaired. The researchers hypothesized that the increase in glucocorticoids induced by psychological stress would cause these adverse effects on skin function.

Study with hairless mice

They tested their hypothesis by subjecting hairless mice to stress while either blocking the production of glucocorticoids or preventing them from acting on the body. The stress was created by placing the mice in small cages in constant light with a radio playing for 48 hours.

Before placing the mice in the stressful situation, the researchers treated one group of mice with RU 486, a substance that blocks the action of glucocorticoids.

A second group of mice received antalarmin, which blocks glucocorticoid production. A third group was subjected to the stress but received neither antalarmin nor RU 486. The fourth group, the control group, remained unstressed in ordinary cages and without the continuous light and sound to which the other groups were exposed.

Results confirm hypothesis

The stressed mice that received RU 486 and antalarmin showed significantly better skin function compared to the stressed mice that did not receive either treatment. The treated mice showed significantly better:

• proliferation
• differentiation
• permeability barrier function
• stratum corneum integrity

The experiment demonstrated the important role that glucocorticoids play in inducing the skin abnormalities brought on by psychological stress. While the researchers hope the study will lead to a way to treat people who suffer these skin conditions, there is still a long way to go: First, the research was done with mice, not people. Second, there may be serious side effects of modulating glucocorticoid activity. Glucocorticoids are essential hormones that play many important roles. Blocking the action of glucocorticoids could have negative outcomes that are much worse than exacerbations in the skin disorders.

The research team is now looking at the effect of psychological stress on the skin's production of antimicrobial peptides, which play a role in defense against infection. They hypothesize that psychological stress might also reduce the ability of the skin to protect from infections.

The National Institutes of Health and the Department of Veterans Affairs Medical Center San Francisco funded the study.