TY - JOUR
T1 - Corticotrophin-releasing factor type 2 receptor-mediated suppression of gonadotrophin-releasing hormone mRNA expression in GT1-7 cells
AU - Kinsey-Jones, James S.
AU - Li, Xiao Feng
AU - Bowe, James E.
AU - Lightman, Stafford L.
AU - O'Byrne, Kevin T.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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 17β-oestradiol (E 2) 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 E 2 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 E 2 on CRF- and stress-induced suppression of the GnRH pulse generator.
AB - 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 17β-oestradiol (E 2) 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 E 2 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 E 2 on CRF- and stress-induced suppression of the GnRH pulse generator.
KW - CRF
KW - CRF-R2
KW - GnRH
KW - GT1-7
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=33845738685&partnerID=8YFLogxK
U2 - 10.1080/10253890601040535
DO - 10.1080/10253890601040535
M3 - Article
C2 - 17175507
AN - SCOPUS:33845738685
SN - 1025-3890
VL - 9
SP - 215
EP - 222
JO - Stress
JF - Stress
IS - 4
ER -