title: Stress-induced inhibition of LH pulses in female rats: role of GABA in arcuate nucleus.
abstract: Stress exerts profound inhibitory effects on reproductive function by suppression of the pulsatile release of GnRH and therefore LH. Besides the corticotrophin-releasing factor (CRF), this effect also might be mediated via GABAergic signaling within the arcuate nucleus (ARC) since its inhibitory effects on LH pulses and increased activity during stress. In the present study, we investigated the role of endogenous GABAergic signaling within the ARC in stress-induced suppression of LH pulses. Ovariectomised oestradiol-replaced rats were implanted with bilateral and unilateral cannulae targeting toward the ARC and lateral cerebral ventricle respectively. Blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for measurement of LH pulses. Intra-ARC infusion of GABAA receptor antagonist, bicuculline (0.2 pmol in 200 nl artificial cerebrospinal fluid (aCSF) each side, three times at 20-min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS; 25 μg/kg i.v.) 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 intra-ARC administration of GABABR antagonist, CGP-35348 (1.5 nmol in 200 nl aCSF each side, three times at 20-min intervals). Moreover, intra-ARC application of either bicuculline or CGP-35348 attenuated the inhibitory effect of CRF (1 nmol in 4 μl aCSF, i.c.v.) on the LH pulses. These data indicate a pivotal and differential role of endogenous GABAA and GABAB signaling mechanisms in the ARC with respect to mediating immunological and psychological stress-induced suppression of the GnRH pulse generator respectively.
authors.affiliation: First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: XiaoFeng
authors.initials: X
authors.lastname: Li
authors.affiliation: First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Shao
authors.affiliation: First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: ChengCheng
authors.initials: C
authors.lastname: Lin
authors.affiliation: First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: O'Byrne
authors.affiliation: First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China First Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDivision of Women's HealthSchool of Medicine, King's College London, Guy's Campus, London, UKDepartment of Surgery LaboratoryFirst Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China linyuanshao@hotmail.com.
authors.forename: YuanShao
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011674:Pulse / Q000379:methods; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C087200:GABA-C receptor; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone; D001640:Bicuculline
keywords: GABA; arcuate nucleus; corticotrophin-releasing factor; luteinizing hormone; stress