GENDER SPECIFICITY IN THE NEURAL REGULATION OF THE RESPONSE TO STRESS- NEW LEADS FROM CLASSICAL PARADIGMS

Pronounced gender-related differences are observable in the regulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) activity under ba sal and stress-related conditions, and by circulating glucocorticoid l evels. This article reviews recent studies that have unequivocally dem onstrated that these differences emerge from the organizational effect s of gonadal steroids during early brain development. Although largely masked by the dominating role of glucocorticoids in maintaining feedb ack thresholds, gonadal steroids continue to exert gender-specific act ivational effects on the LHPA axis through adulthood. The importance o f these modulatory effects of gonadal steroids may be reflected in gen der differences in the incidence of psychopathologies that are accompa nied by symptoms of LHPA dysregulation. One goal of this review is to highlight the need for further investigations into the (still elusive) cellular and molecular mechanisms underlying the activational effects of sex steroids, which may provide leads for neuroprotective hormone replacement strategies.