Role of corticotropin-releasing factor receptor-2 in stress-induced suppression of pulsatile luteinizing hormone secretion in the rat.
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.
Li
Xiao Feng
XF
Division of Reproductive Health, Endocrinology, and Development, New Hunt's House, King's College London, London SE1 1UL, United Kingdom.
Bowe
James E
JE
Lightman
Stafford L
SL
O'Byrne
Kevin T
KT
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
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