title: Differential role of corticotrophin-releasing factor receptor types 1 and 2 in stress-induced suppression of pulsatile luteinising hormone secretion in the female rat.
abstract: Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF(2)) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF(1)) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF(1) and CRF(2) in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 microl) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 microg/kg). All three stressors suppressed LH pulses. The CRF(1) antagonist SSR125543Q (11.5 micromol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF(2) antagonist astressin(2)-B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF(2) while restraint stress-induced inhibition of LH pulses involves both CRF(1) and CRF(2).
authors.affiliation: Division of Reproductive Health, Endocrinology and Development, King's College London, Guy's Campus, London, UK.
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: J E
authors.initials: JE
authors.lastname: Bowe
authors.forename: J S
authors.initials: JS
authors.lastname: Kinsey-Jones
authors.forename: S D
authors.initials: SD
authors.lastname: Brain
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.forename: K T
authors.initials: KT
authors.lastname: O'Byrne
mesh_terms: D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D007003:Hypoglycemia / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000097:blood* / Q000276:immunology; D013315:Stress, Psychological / Q000097:blood; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D008070:Lipopolysaccharides; D018019:Receptors, Corticotropin-Releasing Hormone; D007987:Gonadotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D007986:Luteinizing Hormone