title: 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 (PrP 0/0) and wild-type (PrP+/+) mice. PrP 0/0 showed hypercorticism during the dark part of day. After acute stress, corticosterone and adrenocorticotropic hormone increased similarly in PrP+/+ and PrP 0/0 mice. Adrenocorticotropic hormone, however, remained elevated in PrP+/+ 0/0 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 PrP 0/0 mice. Thus, PrPC may play a role in the negative feedback regulation of axis.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: José R
authors.initials: JR
authors.lastname: Criado
authors.forename: Izabella
authors.initials: I
authors.lastname: Klein
authors.forename: Gianluca
authors.initials: G
authors.lastname: Moroncini
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005838:Genotype; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011863:Radioimmunoassay; D012149:Restraint, Physical / Q000379:methods / Q000523:psychology; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D018621:PrPC Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
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