PMID- 10614646
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 141
IP  - 1
DP  - 2000 Jan
TI  - Urocortin expression in the Edinger-Westphal nucleus is up-regulated by stress
      and corticotropin-releasing hormone deficiency.
PG  - 256-63
AB  - Urocortin is a 40-amino acid mammalian peptide related to CRH and urotensin. The 
      physiological role of urocortin is unknown, but it has been postulated to serve
      some of the functions previously attributed to CRH. We had earlier found that
      urocortin messenger RNA (mRNA) expression within the mouse brain is confined to
      the region of the Edinger-Westphal (EW) nucleus of the midbrain. To further
      characterize the regulation of the urocortin gene, we first cloned and sequenced 
      the mouse gene, confirming the presence of a single gene in the murine genome. A 
      general survey of mouse tissues using Northern blot analysis revealed the
      presence of urocortin mRNA only within the midbrain. By in situ hybridization
      analysis, we found that urocortin mRNA expression in the EW nucleus is responsive
      to stress, as mRNA levels increased approximately 3-fold after 3 h of restraint. 
      Chronic glucocorticoid treatment, although not affecting basal levels, blocked
      the stress-induced rise in urocortin mRNA. Using CRH-deficient [knockout (KO)]
      mice, we examined the effect of combined CRH and glucocorticoid deficiency upon
      urocortin mRNA expression. As in wild-type (WT) mice, we had previously found
      that urocortin expression in CRHKO mouse brain was not detected outside of the EW
      nucleus. However, we found that urocortin expression within the EW of CRHKO mice 
      is up-regulated 2- to 3-fold compared with that in WT mice. This up-regulation is
      not due to a lack of inhibition by glucocorticoids, as urocortin mRNA levels in
      the EW nucleus of CRHKO mice did not change after glucocorticoid supplementation.
      As the EW does not project to any brain regions known to be involved in the
      behavioral responses to stress, urocortin expressed in this site is unlikely to
      mediate stress-induced behaviors. On the other hand, as the EW nucleus may play a
      role in the regulation of the autonomic nervous system and projects to various
      brain stem nuclei that express the CRH receptor, urocortin originating in the EW 
      may play a role in the regulation of the autonomic nervous system during stress.
FAU - Weninger, S C
AU  - Weninger SC
AD  - Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital, 
      Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Peters, L L
AU  - Peters LL
FAU - Majzoub, J A
AU  - Majzoub JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Messenger)
RN  - 0 (Urocortins)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Southern
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - Corticosterone/pharmacology
MH  - Corticotropin-Releasing Hormone/*biosynthesis/*deficiency/genetics
MH  - In Situ Hybridization
MH  - Mesencephalon/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Stress, Psychological/*metabolism
MH  - Up-Regulation
MH  - Urocortins
EDAT- 1999/12/30 00:00
MHDA- 1999/12/30 00:01
CRDT- 1999/12/30 00:00
PHST- 1999/12/30 00:00 [pubmed]
PHST- 1999/12/30 00:01 [medline]
PHST- 1999/12/30 00:00 [entrez]
AID - 10.1210/endo.141.1.7277 [doi]
PST - ppublish
SO  - Endocrinology. 2000 Jan;141(1):256-63. doi: 10.1210/endo.141.1.7277.