Pituitary-adrenocortical response following repeated adrenocorticotropin secretagogue administration in the rat

In the adult male Wistar rat with a pharmacological block of endogenous CRF release, exogenous CRH (0.3 μg/kg iv), administered 15 or 30 min after a first equal dose, was unable to further stimulate adrenocortical activity above the level attained with the first peptide injection. This pituitary-adrenocortical refractoriness towards CRH was not evident when the second CRH injection was performed 60 min after the first. In the same experimental conditions, exogenous vasopressin (AVP) (0.3 μg/kg iv) did not produce any adrenocortical activation. However, AVP (0.3 μg/kg iv), injected 15 min after a first similar dose, induced a small increase in plasma corticosterone concentrations. CRH pretreatment was found to greatly potentiate the adrenocortical effect of AVP injected 15-105 min later. These results, while confirming the refractoriness of the pituitary to response to CRH after a prior stimulation with the same secretagogue, indicate that the adrenocortical response to CRH is regained 60 min after the first stimulation. Moreover, CRH activates a mechanism that greatly potentiates the secretagogue effect of AVP for a considerable time.