High levels of stress hormones stop the mouse from growing


W.When people are stressed, they often experience hair loss. This condition, known as telogen effluvium, results from dormant hair follicles. However, the molecular cause of this switch is unknown.

To solve this puzzle, Harvard University stem cell biologist Ya-Chieh Hsu and her colleagues turned to mice. They first confirmed the effects of stress by exposing mice to unpredictable ailments such as tilting their cages or blinking room lights, and actually found that the animals grew less hair than non-stressed animals. The researchers then conducted a series of experiments to examine the physiological effects of stress in more detail and found wide-ranging signals from the endocrine glands, via the kidneys, to cells in the skin. The group published its results on March 31 in nature.

“This is the first paper that identifies that [mechanistic] Link between stress hormones and hair growth, ”says Rui Yi, a hair follicle stem cell biologist at Northwestern University’s Feinberg School of Medicine, who reviewed the paper and made an accompanying comment in it nature. “And it really uses genetic tools to determine the responsible cell and gene. I find that really remarkable. “

Hsu says she has long been interested in how stress affects skin and hair. Last year, for example, her group found that stress can cause hair to turn gray by triggering signals in the sympathetic nervous system that decrease the number of melanocyte stem cells that give hair its color. Next, her group set out to understand how stress can cause hair loss.

Previous work has shown that removing the adrenal glands from animals such as rats and rabbits promotes hair growth. In this latest study, Hsu’s group found that this was also the case in mice, and observed that animals whose glands had been removed grew more hair on their backs than mice with intact glands. In particular, the hair follicles, which normally alternate between a resting phase known as telogen and a growth phase known as anagen, had shorter telogen phases and longer anagen phases in mice without adrenal glands.

Hsu notes that the group was surprised that removing the adrenal glands from mice resulted in the stem cells of the mice’s hair follicles entering a nearly constant growth phase, even as the animals grew older. “These results suggest that even the basic level of the stress hormone that normally circulates in the body is an important regulator of the resting phase,” she says The scientist in an email.

Corticosterone suppresses the production of GAS6 by dermal papilla cells (green) and thus prevents the activation of hair follicle stem cells. The U-shaped structures over the dermal papilla cells with their glucocorticoid receptors stained magenta are two stem cells.

HSU LAB, HARVARD UNIVERSITY

Looking at the animals’ circulating hormones, the team concluded that corticosterone, an analogue of human cortisol, likely played a role – mice without adrenal glands had almost undetectable levels of the molecule. Feeding non-stressed mice with corticosterone reduced hair growth.

When Hsu and her colleagues suppressed expression of the gene that encodes the glucocorticoid receptor that binds corticosterone to hair follicle stem cells, they saw no change in hair growth, suggesting that the stem cells did not respond directly to changes in corticosterone levels. The researchers then tried to break down the receptor on fibroblasts in and around the hair follicle and identified supporting cells, so-called dermal papilla cells, which convert the corticosterone signal into the regulation of hair growth. Specifically, corticosterone prevents these cells from releasing a protein called GAS6, which activates stem cells to grow hair. Mice treated for overexpression Gas6 had active stem cells and noticeable hair growth, even under stressful conditions, which caused decreased coat growth in control mice.

“In recent years, this lab has been studying some of the most fascinating phenomena about hair follicles that have long been appreciated but not molecularly understood,” said Elaine Fuchs, a stem cell biologist at Rockefeller University who was not involved in the study, writes in an email. “They show that cortisone, produced by the adrenal glands and circulated through the bloodstream in response to chronic stress, significantly affects the papillae, a specialized population of mesenchymal cells needed to stimulate hair growth.”

“It’s a very nice study,” says Yi. “It is very complete when you walk away from the organ and find that there is a hormone molecule and then find out what type of cell it is [is] react to it and then to the molecular mechanism. “

How the results affect humans remains to be seen, and there are some key differences between mouse and human hair growth that need to be considered, Yi says. While a human hair can remain in the growth phase for years, then rest and grow back for a few weeks or months, the mouse hair only grows a few weeks before resting for longer and longer periods of time while moving through rest and growth .

“That’s why we almost always close [the] Hair salon; We can actually estimate our hair growth over time. . . . You never see anyone say, “We’re going to cut mouse hair,” notes Yi. Another contrast to humans is that mouse hairs grow less, but “don’t fall off either”.

So the question remains: what happens in people with telogen discharge, in whom the hair not only stops growing, but also loses its anchorage and falls out? To be able to closely monitor fur growth, Hsu and her colleagues shaved their mice, which made it difficult to say whether hair from follicles that have been in prolonged periods of rest will actually fall out, but Hsu suspects that this would happen at some point.

There is “still a long way to go,” she writes, but says that she and her colleagues “are excited about the potential of Gas6 to increase stem cell activity in hair follicles and [about] Investigation of its relevance and effect on human skin. “

S. Choi et al., “Corticosterone Inhibits GAS6 to Control the Quiet of the Hair Follicle Stem Cells”. nature, doi: 10.1038 / s41586-021-03417-2, 2021.



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