TY - JOUR
T1 - Switching of NR5A proteins associated with the inhibin α-subunit gene promoter after activation of the gene in granulosa cells
AU - Weck, Jennifer
AU - Mayo, Kelly E.
PY - 2006/5
Y1 - 2006/5
N2 - The inhibin α-subunit gene is transcriptionally activated by FSH in ovarian granulosa cells during follicular growth. We have investigated the roles of the NR5A family nuclear receptors steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1) in transcriptional activation of the inhibin α-subunit gene. Transfection assays using an inhibin α-subunit promoter reporter in GRMO2 granulosa cells show that LRH-1 and SF-1 act similarly to increase promoter activity, and that the activity of both transcription factors is augmented by the coactivators cAMP response element-binding protein-binding protein and steroid receptor coactivator 1. However, chromatin immunoprecipitation experiments illustrate differential dynamic association of LRH-1 and SF-1 with the α-subunit inhibin promoter in both primary cells and the GRMO2 granulosa cell line such that hormonal stimulation of transcription results in an apparent replacement of SF-1 with LRH-1. Transcriptional stimulation of the inhibin α-subunit gene is dependent on MAPK kinase activity, as is the dynamic association/dis-association of SF-1 and LRH-1 with the promoter. Inhibition of the phosphatidylinositol 3-kinase signaling pathway influences promoter occupancy and transcriptional activation by SF-1 but not LRH-1, suggesting a possible mechanistic basis for the distinct functions of these NR5A proteins in inhibin α-subunit gene regulation.
AB - The inhibin α-subunit gene is transcriptionally activated by FSH in ovarian granulosa cells during follicular growth. We have investigated the roles of the NR5A family nuclear receptors steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1) in transcriptional activation of the inhibin α-subunit gene. Transfection assays using an inhibin α-subunit promoter reporter in GRMO2 granulosa cells show that LRH-1 and SF-1 act similarly to increase promoter activity, and that the activity of both transcription factors is augmented by the coactivators cAMP response element-binding protein-binding protein and steroid receptor coactivator 1. However, chromatin immunoprecipitation experiments illustrate differential dynamic association of LRH-1 and SF-1 with the α-subunit inhibin promoter in both primary cells and the GRMO2 granulosa cell line such that hormonal stimulation of transcription results in an apparent replacement of SF-1 with LRH-1. Transcriptional stimulation of the inhibin α-subunit gene is dependent on MAPK kinase activity, as is the dynamic association/dis-association of SF-1 and LRH-1 with the promoter. Inhibition of the phosphatidylinositol 3-kinase signaling pathway influences promoter occupancy and transcriptional activation by SF-1 but not LRH-1, suggesting a possible mechanistic basis for the distinct functions of these NR5A proteins in inhibin α-subunit gene regulation.
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U2 - 10.1210/me.2005-0199
DO - 10.1210/me.2005-0199
M3 - Article
C2 - 16423880
AN - SCOPUS:33746564525
SN - 0888-8809
VL - 20
SP - 1090
EP - 1103
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 5
ER -