Chronic stress enhances vasopressin but not corticotropin-releasing factor secretion during hypoglycemia

Quantitative immunocytochemistry was used to investigate the effect of chronic intermittent stress on the storage and release of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the zona externa of the median eminence (ZEME). Wistar rats were subjected to repeated once daily insulin stress and studied 24 h after the last episode of hypoglycemia. Chronic intermittent hypoglycemia differentially affected CRF immuno-staining (CRFi) and AVPi stores in the ZEME, characterized by a transitory fall in CRFi (7 days) and a gradual increase in AVPi (11 days). The acute hypothalamic response to stress was studied by measuring insulin-induced depletion of CRFi and AVPi in the ZEME after blockade of fast axonal transport with colchicine (5 micrograms/rat ic). Three hours after insulin, CRFi was reduced by 24 and 28% in naive and repeatedly (11 times) stressed animals, respectively. In contrast, insulin did not affect CRFi in rats exposed to hypoglycemia for 7 days. In addition, hypoglycemia reduced AVPi in the ZEME by 37, 42, and 54% in naive and repeatedly (7 and 11 times) stressed rats, respectively. We conclude that chronic intermittent hypoglycemia induces a shift in hypothalamic signals for adrenocorticotropic hormone release in favor of AVP. This may result in altered sensitivity of the corticotrophs for hypophysiotropic factors and corticosteroids that are of physiological importance for the pituitary response to subsequent stressors.