Steroid-Independent Activation of ER by GnRH in Gonadotrope Pituitary Cells

In the rat pituitary gland the mechanism responsible for ERα regulation has not been fully elucidated. Using transient transfection assays in αT3–1 cells, a cell line of gonadotrope origin, we show that GnRH stimulates estrogen response element-containing promoters in an estrogen-independent manner....

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2001-08, Vol.142 (8), p.3340-3347
Main Authors: Demay, F, De Monti, M, Tiffoche, C, Vaillant, C, Thieulant, M. L
Format: Article
Language:English
Subjects:
17β-Estradiol
Antiestrogens
Cell activation
Cell lines
Estrogen receptors
Estrogens
Gene regulation
Gonadotropin-releasing hormone
MAP kinase
Pituitary
Pituitary (anterior)
Pituitary gland
Protein kinase C
Reporter gene
Sex hormones
Signal transduction
Transfection
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Summary:In the rat pituitary gland the mechanism responsible for ERα regulation has not been fully elucidated. Using transient transfection assays in αT3–1 cells, a cell line of gonadotrope origin, we show that GnRH stimulates estrogen response element-containing promoters in an estrogen-independent manner. This effect was strictly ER and GnRH receptor dependent, as no activation of the reporter gene was observed in presence of the anti-estrogen ICI 182,780 or a GnRH antagonist. These data suggest that the GnRH-triggered signaling pathway results in 17β-estradiol-independent trans-activation of the ERα in αT3–1 cells. Furthermore, an additive activation was achieved when cells were treated with both GnRH and 17β-estradiol. In primary pituitary cells, GnRH alone (100 nm) did not cause a significant stimulation of reporter gene activity, presumingly due to the low amount of gonadotropes. Interestingly, the combination of 17β-estradiol and GnRH resulted in a significant increase in ERα trans-activation compared with that in cells treated with 17β-estradiol alone. This enhancement was prevented by ICI 182,780, showing an ERα requirement. Moreover, we show that the effects of GnRH on ERα transcriptional activity in gonadotrope cell lines are mediated by the PKC/MAPK pathway. In conclusion, our data demonstrate that GnRH is an important signal in the regulation of ERα trans-activation in gonadotrope cells.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.142.8.8337