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Study points to why stress may affect women more

June 15, 2010
Courtesy of Children's Hospital of Philadelphia
and World Science staff

There may be a bi­o­log­i­cal rea­son why more wom­en than men suf­fer stress-related psy­chi­at­ric dis­or­ders, a study sug­gests.

Stud­y­ing stress sig­nal­ing mo­le­cules in rat brains, re­search­ers found that fe­males are more sen­si­tive than males to low lev­els of a ma­jor stress hor­mone, and less able to adapt to high lev­els of it.

Stud­y­ing stress sig­nal­ing mo­le­cules in rat brains, re­search­ers found that fe­males are more sen­si­tive than males to low lev­els of a ma­jor stress hor­mone, and less able to adapt to high lev­els.


“This is the first ev­i­dence for sex dif­fer­ences” in this sig­nal­ing sys­tem, said study lead­er Rita J. Val­en­ti­no, a be­hav­ior­al neu­ro­sci­ent­ist at The Chil­dren’s Hos­pi­tal of Phil­a­del­phia. Her re­search ap­peared on­line June 15 in the re­search jour­nal Mo­lec­u­lar Psy­chi­a­try.

The gen­der dif­fer­ences, she ex­plained, in­volve the way mo­lec­u­lar struc­tures on brain cell sur­faces, called re­cep­tors, han­dle the traf­fic of stress sig­nal­ing molecules. “Although more re­search is cer­tainly nec­es­sary to de­ter­mine wheth­er this trans­lates to hu­mans, this may help to ex­plain why wom­en are twice as vulnera­ble as men to stress-related dis­or­ders,” she added.

Wom­en have a high­er in­ci­dence of de­pres­sion, post-traumatic stress dis­or­der, and oth­er anx­i­e­ty dis­or­ders, said Val­en­ti­no. 

Her re­search fo­cus­es on corticotropin-releasing fac­tor, or CRF, a hor­mone that or­ga­nizes stress re­sponses in mam­mals. An­a­lyz­ing the brains of rats put through a swim stress test, Val­en­ti­no’s team found that in fe­male rats, brain cells had re­cep­tors for CRF that at­tached more tightly to cell sig­nal­ing pro­teins than in male rats. The re­cep­tors thus re­sponded more strongly to the stress hor­mone.

Fur­ther­more, Val­en­ti­no said, stressed male rats dis­played an adaptive re­sponse, called in­ter­nal­iz­a­tion, in their brain cells. These cells re­duced the num­ber of CRF re­cep­tors, and be­came less re­spon­sive to the hor­mone. In fe­male rats this did­n’t hap­pen be­cause a spe­cif­ic pro­tein did not link up with the CRF re­cep­tor in a way that was needed for this adapta­t­ion, Val­en­ti­no ex­plained.

“We can­not say that the bi­o­log­i­cal mech­an­ism is the same in peo­ple,” she added, not­ing that oth­er mech­an­isms and hor­mones play roles in hu­man stress. But “re­search­ers al­ready know that CRF regula­t­ion is dis­rupted in stress-related psy­chi­at­ric dis­or­ders, so this re­search may be rel­e­vant to the un­der­ly­ing hu­man bi­ol­o­gy.”


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There may be a biological reason why more women than men suffer stress-related psychiatric disorders, a study suggests. Studying stress signaling molecules in animal brains, researchers found that females are more sensitive than males to low levels of a major stress hormone, and less able to adapt to high levels. “This is the first evidence for sex differences” in this signaling system, said study leader Rita J. Valentino, a behavioral neuroscientist at The Children’s Hospital of Philadelphia. Her research appeared online June 15 in the research journal Molecular Psychiatry. The gender differences, she explained, involve the way molecular structures on brain cell surfaces, called receptors, handle the traffic of stress signaling molecules. “Although more research is certainly necessary to determine whether this translates to humans, this may help to explain why women are twice as vulnerable as men to stress-related disorders,” she added. Women have a higher incidence of depression, post-traumatic stress disorder, and other anxiety disorders, said Valentino. Her research focuses on corticotropin-releasing factor, or CRF, a hormone that organizes stress responses in mammals. Analyzing the brains of rats put through a swim stress test, Valentino’s team found that in female rats, brain cells had receptors for CRF that attached more tightly to cell signaling proteins than in male rats. The receptors thus responded more strongly to the stress hormone. Furthermore, Valentino said, stressed male rats displayed an adaptive response, called internalization, in their brain cells. These cells reduced the number of CRF receptors, and became less responsive to the hormone. In female rats this didn’t happen because a specific protein did not link up with the CRF receptor in a way that was needed for this adaptation, Valentino explained. “We cannot say that the biological mechanism is the same in people,” she added, noting that other mechanisms and hormones play roles in human stress. But “researchers already know that CRF regulation is disrupted in stress-related psychiatric disorders, so this research may be relevant to the underlying human biology.”