PMID- 24578294
OWN - NLM
STAT- MEDLINE
DCOM- 20140630
LR  - 20220129
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 221
IP  - 2
DP  - 2014 May
TI  - Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing 
      hormone.
PG  - 337-46
LID - 10.1530/JOE-13-0603 [doi]
AB  - Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus 
      incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 
      binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the 
      hypothalamic paraventricular nucleus (PVN), an area central to the stress 
      response. The physiological function of relaxin-3 is unknown but previous work 
      suggests a role in appetite control, stimulation of the 
      hypothalamic-pituitary-gonadal axis and stress. Central administration of 
      relaxin-3 induces c-fos expression in the PVN and increases plasma ACTH levels in 
      rats. The aim of this study was to investigate the effect of central 
      administration of human relaxin-3 (H3) on the hypothalamic-pituitary-adrenal 
      (HPA) axis in male rodents in vivo and in vitro. Intracerebroventricular (i.c.v) 
      administration of H3 (5 nmol) significantly increased plasma corticosterone at 
      30 min following injection compared with vehicle. Intra-PVN administration of H3 
      (1.8-1620 pmol) significantly increased plasma ACTH at 1620 pmol H3 and 
      corticosterone at 180-1620 pmol H3 at 30 min following injection compared with 
      vehicle. The stress hormone prolactin was also significantly raised at 15 min 
      post-injection compared with vehicle. Treatment of hypothalamic explants with H3 
      (10-1000 nM) stimulated the release of corticotrophin-releasing hormone (CRH) and 
      arginine vasopressin (AVP), but H3 had no effect on the release of ACTH from in 
      vitro pituitary fragments. These results suggest that relaxin-3 may regulate the 
      HPA axis, via hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central 
      signal linking nutritional status, reproductive function and stress.
FAU - McGowan, B M
AU  - McGowan BM
AD  - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation 
      Trust, Westminster Bridge Road, London SE1 7EH, London Section of Investigative 
      Medicine, Department of Medicine, Imperial College London, 6th Floor Commonwealth 
      Building, Hammersmith Campus, Du Cane Road, London W12 ONN, UK Molecular 
      Genetics, Rockefeller University, New York, NY 10065, USA.
FAU - Minnion, J S
AU  - Minnion JS
FAU - Murphy, K G
AU  - Murphy KG
FAU - Roy, D
AU  - Roy D
FAU - Stanley, S A
AU  - Stanley SA
FAU - Dhillo, W S
AU  - Dhillo WS
FAU - Gardiner, J V
AU  - Gardiner JV
FAU - Ghatei, M A
AU  - Ghatei MA
FAU - Bloom, S R
AU  - Bloom SR
LA  - eng
GR  - BB/E52708X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/I00842X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140512
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RLN3 protein, rat)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9002-69-1 (Relaxin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/metabolism
MH  - Animals
MH  - Corticosterone/metabolism
MH  - Corticotropin-Releasing Hormone/*physiology
MH  - Down-Regulation/drug effects
MH  - Hypothalamo-Hypophyseal System/drug effects/metabolism
MH  - Injections, Intraventricular
MH  - Male
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Neurosecretory Systems/*drug effects/metabolism
MH  - Pituitary-Adrenal System/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Relaxin/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Stress, Physiological/*drug effects
OTO - NOTNLM
OT  - ACTH
OT  - RXFP1
OT  - RXFP3
OT  - corticosterone
OT  - paraventricular nucleus
OT  - relaxin-3
EDAT- 2014/03/01 06:00
MHDA- 2014/07/01 06:00
CRDT- 2014/03/01 06:00
PHST- 2014/03/01 06:00 [entrez]
PHST- 2014/03/01 06:00 [pubmed]
PHST- 2014/07/01 06:00 [medline]
AID - JOE-13-0603 [pii]
AID - 10.1530/JOE-13-0603 [doi]
PST - epublish
SO  - J Endocrinol. 2014 May 12;221(2):337-46. doi: 10.1530/JOE-13-0603. Print 2014 
      May.