Untitled

Stress Effects on the Developing Brain 131Recently, four roles for glucocorticoids have been posited that help reduce confusionover the functions of glucocorticoids in stress: permissive, stimulatory, suppressive,and preparatory (see review, Sapolsky, Romero, & Munck, 2000). Thepermissive role is served by the impact of glucocorticoids operating through mineralocorticoidreceptors (MR) that are stimulated at basal or nonstress ranges ofthe hormone. These functions include helping nerve cells remain responsive totheir neurotransmitters and facilitating glucose uptake by cells. Interestingly, disorderslike chronic fatigue and chronic pain syndromes have been associated withremarkably low basal glucocorticoid concentrations and problems in increasingglucocorticoids to stressors. This may reflect low occupation of MR by glucocorticoidsin these patients. The stimulatory role is captured by the ability of glucocorticoidsto liberate energy stores, increasing the glucose available for action.Notably, adrenaline from the SAM system also serves this function but producesthis glucose-liberating effect much more quickly than can stress increases in glucocorticoids.This is one reason that the SAM system is viewed as mobilizing energyresources for rapid response, whereas the HPA system is viewed as mobilizingenergy resources for prolonged periods of threat.The suppressive role of glucocorticoids involves their inhibitory impact on manyof the events set into motion by the SAM system and other elements of the stressemotionsystem. These suppressive effects of glucocorticoids operate throughglucocorticoid receptors (GR), the receptors that become activated once glucocorticoidsare in stress ranges (or at the peak of the daily basal cycle). Suppressiveeffects of glucocorticoids include such things as reducing the cells ability totake up glucose, increasing the production of excitatory amino acids in nerve cells,and interfering with activity of the immune system. Suppressive effects, althoughthey would seem quite counterproductive, are argued to be highly important becausethey check, reverse, or contain other stress-related effects, preventing themfrom “overshooting.” This may be seen in posttraumatic stress disorder, in whichthe emergence of the disorder may be related to a failure to mount a strong glucocorticoidresponse to the traumatic event (Yehuda, 2000). However, like any otherpowerful suppressive system, just enough tends to support healthy functioning,whereas too much tends to impair functioning. For example, an acute and shortlivedstress response of the HPA axis may help prevent the immune system from“overshooting,” but prolonged stress activation of the HPA axis may chronicallysuppress immune functioning, increasing susceptibility to infections. Similarly,an acute and short-lived stress response of the HPA system may allow nerve cellsin the hippocampus to respond more intensely and lay down emotional memoriesmore effectively, but a prolonged HPA stress response may produce cell deathand fewer connections among nerve cells in the hippocampus (McEwen et al., 1992;Strand, 1999).Finally, preparatory effects involve the ability of glucocorticoids to alter geneexpression in ways that then alter responses to subsequent stressors. This function