Hypothalamic–pituitary–adrenal axis disregulation in PrPC-null mice

Abstract

As manifestations of prion diseases include disturbances of hypothalamic and pituitary functions, we tested the hypothesis that the cellular prion protein (PrPC) has a role as modulator of the hypothalamic–pituitary–adrenal axis. The level of corticosterone and adrenocorticotropic hormone were compared in PrPC null (PrP0/0) and wild-type (PrP+/+) mice. PrP0/0 showed hypercorticism during the dark part of day. After acute stress, corticosterone and adrenocorticotropic hormone increased similarly in PrP+/+ and PrP0/0 mice. Adrenocorticotropic hormone, however, remained elevated in PrP0/0 mice at corticosterone levels that are inhibitory in PrP+/+ mice. Pretreatment with corticosterone or dexamethasone inhibited stress-induced elevation of adrenocorticotropic hormone in PrP+/+ but not in PrP0/0 mice. Thus, PrPC may play a role in the negative feedback regulation of axis.