Ligand-independent activation of pituitary ER: Dependence on PKA-stimulated pathways

D. A. Schreihofer, E. M. Resnick, V. Y. Lin, M. A. Shupnik

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

In pituitary and other target tissues, estrogen acts through ERs, which are ligand-activated nuclear transcription factors. ERs can also be activated by intracellular signaling pathways in a ligand-independent manner in some cells. Because the pituitary is the target of several cAMP-activating factors, we examined the ability of cAMP to activate ERs in the αT3 gonadotrope cell line. Forskolin, 8-bromo-cAMP, and pituitary adenylate cyclase-activating polypeptide all enhanced ER-dependent promoter activity, which was inhibited by antiestrogen or a pituitary-specific inhibitory ER variant. Activation was PKA dependent and was blocked by the PKA inhibitor H89 or cotransfection of the inhibitor PKI. Although cAMP activated MAPK in αT3 cells, inhibition of MAPK with the MEK inhibitor PD98059 did not prevent forskolin-induced ER activation. Similarly, epidermal growth factor did not stimulate ER activity, although it increased MAPK activation. Forskolin-induced activation of ER was enhanced by cotransfection of steroid receptor coactivator-1 and was inhibited by the repressor of ER action, suggesting that cAMP does not alter the normal interactions between ER and cofactors. In contrast to results with estrogen, cAMP treatment did not decrease ER protein levels. These results demonstrate that in the pituitary, cAMP activates ER in a ligand-independent manner exclusively through PKA.

Original languageEnglish
Pages (from-to)3361-3368
Number of pages8
JournalEndocrinology
Volume142
Issue number8
DOIs
StatePublished - 1 Jan 2001

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Colforsin
Ligands
Estrogens
Nuclear Receptor Coactivator 1
Pituitary Adenylate Cyclase-Activating Polypeptide
8-Bromo Cyclic Adenosine Monophosphate
Estrogen Receptor Modulators
Mitogen-Activated Protein Kinase Kinases
Epidermal Growth Factor
Transcription Factors
Cell Line
Proteins

Cite this

Schreihofer, D. A. ; Resnick, E. M. ; Lin, V. Y. ; Shupnik, M. A. / Ligand-independent activation of pituitary ER : Dependence on PKA-stimulated pathways. In: Endocrinology. 2001 ; Vol. 142, No. 8. pp. 3361-3368.
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Ligand-independent activation of pituitary ER : Dependence on PKA-stimulated pathways. / Schreihofer, D. A.; Resnick, E. M.; Lin, V. Y.; Shupnik, M. A.

In: Endocrinology, Vol. 142, No. 8, 01.01.2001, p. 3361-3368.

Research output: Contribution to journalArticle

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