Stress alters cutaneous permeability barrier homeostasis.
Recent studies have shown that psychological stress can influence cutaneous barrier function, suggesting that this form of stress could trigger or aggravate skin disease. In the present study, we demonstrate that transfer of hairless mice to a different cage delays barrier recovery rates. Pretreatment with a phenothiazine sedative, chlorpromazine, before transfer of animals restored the kinetics of barrier recovery toward normal, suggesting that psychological stress is the basis for this alteration in barrier homeostasis. To determine the mechanism linking psychological stress to altered barrier recovery, we first demonstrated that plasma corticosterone levels increase markedly after transfer of animals to new cages and that pretreatment with chlorpromazine blocks this increase. Second, we demonstrated that the systemic administration of corticosterone delays barrier recovery. Finally, we demonstrated that pretreatment with the glucocorticoid receptor antagonist RU-486 blocks the delay in barrier recovery produced by systemic corticosterone, change of cage, or immobilization. These results suggest that psychological stress stimulates increased production of glucocorticoids, which, in turn, adversely affects permeability barrier homeostasis.
Denda
M
M
Shiseido Research Center, Yokohama, 236-8643 Japan. mirsuhiro.denda@to.shiseido.co.jp
Tsuchiya
T
T
Elias
P M
PM
Feingold
K R
KR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006799:Housing, Animal; D007103:Immobilization; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D015735:Mifepristone / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
D014150:Antipsychotic Agents; D006727:Hormone Antagonists; D015735:Mifepristone; D002746:Chlorpromazine; D003345:Corticosterone