The role of the locus coeruleus in corticotropin-releasing hormone and stress-induced suppression of pulsatile luteinizing hormone secretion in the female rat.

Abstract:

:Despite a wealth of evidence for CRH mediating stress-induced suppression of the hypothalamic GnRH pulse generator, and hence reproductive dysfunction, the site and mechanism of action remains elusive. The locus coeruleus (LC), a prominent noradrenergic brain stem nucleus, is innervated by CRH neurons, mediates several behavioral stress responses, and is implicated in the control of pulsatile LH secretion. The aim of this study was to test the hypothesis that LC CRH has a critical role in mediating stress-induced suppression of pulsatile LH secretion in the rat. Ovariectomized rats with 17beta-estradiol or oil-filled s.c. capsules were implanted with bilateral LC and i.v. cannulae. Central administration of CRH (10 ng to 1 microg) resulted in a dose-dependent suppression of LH pulses, which was reversed by a CRH receptor antagonist (alpha-helical CRF(9-41), 1 microg). The induction of c-fos expression in glutamic acid decarboxylase67 immunostained neurons in the preoptic area suggests activation of the secretion of gamma-aminobutyric acid in response to intracoerulear administration of CRH; 17beta-estradiol further increased the percentage of glutamic acid decarboxylase67-positive neurons that expressed fos and augmented suppression of LH pulses. Furthermore, intracoerulear administration of alpha-helical CRF(9-41) completely blocked restraint stress-induced suppression of LH pulses, without affecting the inhibitory response to hypoglycemia. These results suggest that CRH innervation of the LC may play a pivotal, but differential, role in the normal physiological response of stress-induced suppression of the GnRH pulse generator and hence the reproductive system.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Mitchell JC,Li XF,Breen L,Thalabard JC,O'Byrne KT

doi

10.1210/en.2004-1053

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

323-31

issue

1

eissn

0013-7227

issn

1945-7170

pii

en.2004-1053

journal_volume

146

pub_type

杂志文章