title: Corticotrophin-releasing factor type 2 receptor-mediated suppression of gonadotrophin-releasing hormone mRNA expression in GT1-7 cells.
abstract: Corticotrophin-releasing factor (CRF) released during stress has been implicated in the suppression of the hypothalamo-pituitary-gonadal (HPG) axis, especially the gonadotrophin-releasing hormone (GnRH) pulse generator, the central neural regulator of pituitary LH and FSH secretion, resulting in reproductive dysfunction. The gonadal steroid 17beta-oestradiol (E2) has been shown to enhance CRF- and stress-induced suppression of pulsatile LH secretion. In the present study, we investigated the potential direct action of CRF on GnRH neurones by using GT1-7 cells, an established GnRH cell line. Furthermore, we investigated the modulatory influence of E2 on the effects of CRF and expression of CRF type 2 receptors (CRF-R2). Expression of CRF-R2 in the GT1-7 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). CRF produced a dose-dependent suppression of GnRH mRNA expression, an effect reversed by the selective CRF-R2 antagonist, astressin2-B (Ast2-B). E2 combined with CRF resulted in a greater suppression of GnRH expression compared with either treatment alone. E2 also increased CRF-R2 expression. These results demonstrate for the first time expression of CRF-R2 in the GT1-7 cells and suggest that CRF may directly regulate GnRH gene expression, an effect mediated, at least in part, by CRF-R2. They also raise the possibility that up-regulation of CRF-R2 may contribute to the sensitising influence of E2 on CRF- and stress-induced suppression of the GnRH pulse generator.
authors.affiliation: Division of Reproduction and Endocrinology, King's College London, London, UK.
authors.forename: James S
authors.initials: JS
authors.lastname: Kinsey-Jones
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; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D007031:Hypothalamus; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone