title: Role of corticotropin-releasing factor receptor-2 in stress-induced suppression of pulsatile luteinizing hormone secretion in the rat.
abstract: Corticotropin-releasing factor (CRF) has been implicated as an important mediator of stress-induced inhibition of reproduction. The role of specific CRF receptor subtypes in this effect is unknown, and in the current study, we investigated the role of the CRF-R2 receptor in stress-mediated suppression of pulsatile LH section. Ovariectomized rats with sc 17beta-estradiol capsules were implanted with intracerebroventricular (i.c.v.) and i.v. cannulae. Blood samples (25 microl) were collected every 5 min for 5 h for LH measurement. Central administration of urocortin II (0.24, 2.4, 24, or 240 nmol, i.c.v.), which selectively binds to CRF-R2, resulted in a dose-dependent suppression of LH pulses. Restraint stress (1 h) induced a profound suppression of pulsatile LH secretion and astressin2-B, a selective CRF-R2 antagonist (28 nmol i.c.v., 10-min prerestraint), was effective in blocking this inhibitory response. These findings suggest that CRF-R2 mediates, at least in part, restraint stress-induced inhibition of LH pulses and may play a pivotal role in the normal physiological response of stress-induced suppression of the hypothalamic GnRH pulse generator and hence the reproductive system.
authors.affiliation: Division of Reproductive Health, Endocrinology, and Development, New Hunt's House, King's College London, London SE1 1UL, United Kingdom.
authors.forename: Xiao Feng
authors.initials: XF
authors.lastname: Li
authors.forename: James E
authors.initials: JE
authors.lastname: Bowe
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Kevin T
authors.initials: KT
authors.lastname: O'Byrne
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*; D054832:Urocortins
chemical_list: C101531:CRF receptor type 2; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C120841:astressin B; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone