Regulation of Estrogen Receptor (ER) Isoform Messenger RNA Expression by Different ER Ligands in Female Rat Pituitary1

Abstract

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 ERalpha and ERbeta isoforms, as well as those for the truncated ERalpha product (TERP), and the variant ERbeta2, 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 ERbeta and ERbeta2 mRNAs, whereas it decreased TERP-1 and -2 levels without affecting those of ERalpha. Administration of estradiol benzoate (as potent agonist for alpha and beta forms of ER) or the selective ERalpha agonist, propyl pyrazole triol, fully reversed the responses to OVX, while the ERbeta ligand, diarylpropionitrile, failed to induce any significant effect except for a partial stimulation of TERP-1 and -2 mRNA expression levels. To note, the ERbeta 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 ERalpha agonist, although the magnitude of tamoxifen effects was significantly lower than those of the ERalpha 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 ERalpha. Differential regulation of ER isoforms may represent a relevant system for the self-tuning of estrogen responsiveness in female pituitary.

Tamoxifen-Induced Anorexia Is Associated With Fatty Acid Synthase Inhibition in the Ventromedial Nucleus of the Hypothalamus and Accumulation of Malonyl-CoA

“…To confirm that TMX was bioactive at hypothalamic levels, we studied the mRNA levels of estrogen receptor ␤ and progesterone receptor of TMX-treated rats. As previously reported, the mRNA expression of estrogen receptor ␤ (40) and progesterone receptor (41) was increased in the hypothalamus after TMX treatment (online appendix Fig. 2).…”

The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

“…These results support the hypothesis that the 3 isoform may play a significant physiological role that is under steroidal control. A recent report indicates that endogenous estrogen differentially regulates pituitary expression of mRNAs encoding several ER isoforms with distinct functional properties (Tena-Sempere et al 2004). This, together with our current results, allows us to postulate that interaction of ER protein with its ligand not only activates signaling but also turns on different mechanisms for the fine tuning of uterine responsiveness to estrogen.…”

Differential expression profiling of estrogen receptor in the ovaries of two egg duck (Anas platyrhynchos) breeds

“…Estrogens play a pivotal role in the development and maintenance of normal sexual and reproductive functions (Heldring et al, 2007;Muriach et al, 2008). The biological action of estrogens is manifested through two high-affinity estrogen receptors, estrogen receptor alpha and estrogen receptor beta, which belong to the family of the transcription factors, the nuclear receptor super family, and are expressed at different levels in target cells (Greene et al, 1986;Kuiper et al, 1996;Gruber et al, 2004;Tean-Sempere et al, 2004). The research results in pregnant swine reported by Knapczyk (2008) suggest that in the regulation of ovarian function during pregnancy estrogen acts both via ESR1 and ESR2 and these are involved in the process of successful reproduction.…”