Gender Differences In The Processing Of Acute And Repeated Stress

Chronic stress is implicated in the pathogenesis of a variety of diseases, including affective, immune and cardiovascular disorders, which are differentially experienced by men and women. Corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and glucocorticoid receptor (GR) are the major regulators of the stress response and are widely expressed in the paraventricular nucleus of the hypothalamus (PVH), where adaptive responses to stress are generated. Adult male and female rats were subjected to single (acute) or 14 consecutive daily (repeated) 30 min restraint sessions, or maintained as unstressed controls. Rats were perfused after their final restraint, and their brain tissues sectioned and stained immunohistochemically for Fos and to co-localize Fos/CRF, Fos/AVP and Fos/GR in the PVH. Control rats expressed low levels of Fos, with females exhibiting significantly fewer Fos positive cells than males. Acute restraint increased the number of Fos-expressing cells in the PVH of both males and females, with a relatively greater increase seen in the males. In repeated restraint stress, Fos returned to levels not significantly different from control in both sexes, and habituated responses were seen following repeated stress. Fos/CRF, Fos/AVP and Fos/GR expression showed similar trends as Fos alone across all experimental groups. Female rats that were ovariectomized (OVX) with or with out estrogen replacement did not show similar trends in stress response for Fos/AVP and Fos/GR as those previously described. OVXed vehicle females showed high basal (control) levels for both Fos/AVP and Fos/GR, in comparison to OVXed control females that had either low or high estrogen replacement. Together, these data suggest that gender-specific responses to stress are evident at the level of neuronal activation, and may in part be due to effects of estrogen