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1 March 2004 Regulation of Estrogen Receptor (ER) Isoform Messenger RNA Expression by Different ER Ligands in Female Rat Pituitary
M. Tena-Sempere, V. M. Navarro, A. Mayen, C. Bellido, J. E. Sánchez-Criado
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Net estrogen sensitivity in target tissues critically depends on the regulated expression of full-length and alternately processed estrogen receptor (ER) isoforms. However, the molecular mechanisms for the control of pituitary responsiveness to estrogen remain partially unknown. In the present communication, we report the ability of different ligands, with distinct agonistic or antagonistic properties at the ER, to modulate the expression of the transcripts encoding ERα and ERβ isoforms, as well as those for the truncated ERα product (TERP), and the variant ERβ2, in pituitaries from ovariectomized rats, i.e., a background devoid of endogenous estrogen. Compared with expression levels at the morning of proestrus, ovariectomy (OVX) resulted in increased pituitary expression of ERβ and ERβ2 mRNAs, whereas it decreased TERP-1 and -2 levels without affecting those of ERα. Administration of estradiol benzoate (as potent agonist for α and β forms of ER) or the selective ERα agonist, propyl pyrazole triol, fully reversed the responses to OVX, while the ERβ ligand, diarylpropionitrile, failed to induce any significant effect except for a partial stimulation of TERP-1 and -2 mRNA expression levels. To note, the ERβ agonist was also ineffective in altering pituitary expression of progesterone receptor-B mRNA, i.e., a major estrogen-responsive target. In all parameters tested, tamoxifen, a selective ER modulator with mixed agonist/antagonist activity, behaved as ERα agonist, although the magnitude of tamoxifen effects was significantly lower than those of the ERα ligand, except for TERP induction. In contrast, the pure antiestrogen RU-58668 did not modify the expression of any of the targets under analysis. Overall, our results indicate that endogenous estrogen differentially regulates pituitary expression of the mRNAs encoding several ER isoforms with distinct functional properties, by a mechanism that is mostly conducted through ERα. Differential regulation of ER isoforms may represent a relevant system for the self-tuning of estrogen responsiveness in female pituitary.

M. Tena-Sempere, V. M. Navarro, A. Mayen, C. Bellido, and J. E. Sánchez-Criado "Regulation of Estrogen Receptor (ER) Isoform Messenger RNA Expression by Different ER Ligands in Female Rat Pituitary," Biology of Reproduction 70(3), 671-678, (1 March 2004).
Received: 19 July 2003; Accepted: 1 October 2003; Published: 1 March 2004
estradiol receptor
mechanisms of hormone action
progesterone receptor
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