Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice.
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.
Sanchez-Alavez
Manuel
M
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
Criado
José R
JR
Klein
Izabella
I
Moroncini
Gianluca
G
Conti
Bruno
B
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
D005938:Glucocorticoids; D018621:PrPC Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
Hypertension. 1994 May;23(5):569-76
8175163
Vet Rec. 2002 Jun 1;150(22):680-4
12074236
Neurodegeneration. 1995 Mar;4(1):113-4
7600180
Endocr Rev. 1984 Winter;5(1):1-24
6323158
Endocrinology. 1984 Jan;114(1):164-9
6317342
J Biol Chem. 2000 Sep 1;275(35):26834-41
10842180
Endocr Rev. 1991 May;12(2):118-34
2070776
J Endocrinol. 2000 May;165(2):527-32
10810317
Endocrinology. 1999 May;140(5):2422-5
10218997
Nature. 1973 Mar 2;242(5392):63-5
4571633
Front Neuroendocrinol. 2003 Jul;24(3):151-80
14596810
Acta Neurobiol Exp (Wars). 2002;62(3):153-66
12416393
Heredity (Edinb). 1962 Feb;17:75-105
14484073
Nature. 1996 Jan 25;379(6563):339-43
8552188
Endocrinology. 1984 Dec;115(6):2368-74
6094157
Endocrinology. 2000 Mar;141(3):988-94
10698174
Mol Neurobiol. 1994 Apr-Jun;8(2-3):121-7
7999308
Brain. 1964 Mar;87:153-76
14152208
J Infect Dis. 1990 Mar;161(3):462-6
2313125
J Neurosci. 1993 Sep;13(9):3839-47
8396170
Eur J Neurosci. 2006 May;23(10):2723-30
16817875
J Mol Biol. 1999 Oct 1;292(4):797-817
10525406
Neuroscience. 1999;91(4):1201-4
10391428
Endocrinol Metab Clin North Am. 2005 Jun;34(2):271-92, vii
15850842