The role of GABAergic signalling in stress-induced suppression of GnRH pulse generator frequency in female rats

YS Lin, XF Li, B Shao, MH Hu, AL Goundry, A Jeyaram, SL Lightman, KT O'Byrne

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)

Abstract

Stress exerts profound inhibitory effects on reproductive function by suppressing the pulsatile release of gonadotrophin-releasing hormone (GnRH), and therefore luteinising hormone (LH). This effect is mediated in part via the corticotrophin-releasing factor (CRF) system, but another potential mechanism is via GABAergic signalling within the medial preoptic area (mPOA) as this has known inhibitory influences on the GnRH pulse generator and shows increased activity during stress. In the present study, we investigated the role of the preoptic endogenous GABAergic system in stress-induced suppression of the GnRH pulse generator. Ovariectomised oestradiol-replaced rats were implanted with bilateral and unilateral cannulae targeting toward the mPOA and lateral cerebral ventricle, respectively; blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for the measurement of LH pulses. Intra-mPOA administration of the specific GABA(A) receptor antagonist, bicuculline (0.2 pmol each side, three times at 20-min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS, 25 μg/kg, intravenous) but not restraint (1 h) stress on pulsatile LH secretion. In contrast, restraint but not LPS stress-induced suppression of LH pulse frequency was reversed by application of the selective GABA(B) receptor antagonist, CGP-35348 into the mPOA (1.5 nmol each side, three times at 20-min intervals). However, intra-mPOA application of either bicuculline or CGP-35348 attenuated the inhibitory effect of CRF (1 nmol, intracerebroventricular) on the pulsatile LH secretion. These data indicate a pivotal and differential role of endogenous GABAergic signalling in the mPOA in mediating psychological and immunological stress-induced suppression of the GnRH pulse generator.
Translated title of the contributionThe role of GABAergic signalling in stress-induced suppression of GnRH pulse generator frequency in female rats
Original languageEnglish
Pages (from-to)477 - 488
Number of pages12
JournalJournal of Neuroendocrinology
Volume24(3)
DOIs
Publication statusPublished - Mar 2012

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