Changes in releasability of ACTH and beta-endorphin with chronic stress

The activation of the hypothalamic pituitary adrenal axis by stress is well-known. Using inescapable intermittent footshock as a stressor in rats, we have previously demonstrated a rise in circulating plasma Beta-endorphin/Beta-LPH which parallels the rise in plasma ACTH, the primary POMC derived peptides released by anterior lobe. In addition, the rise in ACTH is accompanied by approximately a tenfold rise in plasma corticosteroids. Short term anterior lobe pituitary cultures from rats who have received inescapable intermittent footshock for 30 minutes show a blunted dose response curves to the ACTH releasing secretagogues arginine vasopressin (AVP) and ovine corticotropin releasing factor (oCRF). Similarly a blunted dose response curves to secretagogues can be seen by either the addition of dexamethasone (0.5 nM) to the culture medium or pretreatment of the rats with 1 mg dexamethasone intraperitoneally 90 minutes prior to decapitation. Thus, glucocorticoids may play a role in the blunted response to secretagogues seen in anterior lobe cultures from acutely stressed rats. We now report that chronically stressed rats exhibit increased releasability of ACTH and Beta-endorphin/Beta-LPH products by oCRF, suggesting an increase of the peptides in the releasable pool.