Disease relevance of ESR2

• ERbeta was present in control CA1 pyramidal neurons, decreasing on day 4 after ischemia [1].
• The novel estrogen receptor ERbeta could be a key factor for proliferation and breast cancer risk [2].

High impact information on ESR2

• E2 alone increased mammary epithelial proliferation by approximately sixfold (P:<0.0001) and increased mammary epithelial estrogen receptor (ERalpha) mRNA expression by approximately 50% (P:<0.0001; ERbeta mRNA was not detected in the primate mammary gland) [3].
• There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERbeta, adds an additional level of complexity [4].
• To determine if ERbeta mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release [4].
• Replacement of progestin activity with R5020 reduced luteal ERbeta mRNA levels to those seen in animals receiving antide + LH [4].
• Thus, there is dynamic ERbeta expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERbeta)-mediated pathway [4].

Chemical compound and disease context of ESR2

• These results indicate that ERbeta is the major receptor responsible for the direct estrogen actions on the monkey hippocampus, regulating glial response after ischemia [1].

Biological context of ESR2

• However, ERbeta mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase [4].
• Full length ERbeta (wild type, ERbeta1) cDNAs were cloned from macaque and marmoset; they encoded proteins of similar size to those found in human (59 and 54 kDa, long and short forms respectively) and shared significant sequence homology (97.5% in macaque and 93.8% in marmoset) with the human peptide sequence [5].

Anatomical context of ESR2

• ERalpha and ERbeta were localized in the myometrium by immunohistochemistry [6].
• Additional regional analyses in female mouse brain with PA1-310B antibody showed that a second, 59 kDa ERbeta-ir band was present in cortex, striatum, hippocampus, and amygdala that could represent one or both of the larger ERbeta variants (530 and 549aa) [7].
• The expression level of the second ERbeta isoform exhibited regional variation, with the strongest immunoreactivity detected in cortex and amygdala [7].
• ER-beta and thromboxane-prostanoid receptor (TPR) were coexpressed in coronary arteries and aorta [8].
• The present data show that long-term hormone treatment affects the ERalpha and ERbeta protein levels in the endometrium [9].

Associations of ESR2 with chemical compounds

• When monkeys also received the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERbeta mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only [4].
• R,R-tetrahydrochrysene, a selective ER-beta antagonist, significantly blocked the E3- and 3beta-Adiol-mediated attenuation of late Ca2+ signal increases [8].
• Together these studies suggest that the serotonin neural system could transduce the action of estrogen via ER beta on aspects of mood and cognition [10].
• This reduction of late Ca2+ signals also appeared after >72 h of treatment with subnanomolar 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an endogenous dihydrotestosterone metabolite with ER-beta binding activity [8].
• This suggests that raloxifene and arzoxifene are agonists at ER beta in the context of the serotonin neuron [10].

Other interactions of ESR2

• ER alpha mRNA did not change, whereas ER beta decreased 12-36 h after the ovulatory stimulus (P < 0.05) [11].

Analytical, diagnostic and therapeutic context of ESR2

• The cloned ERbeta PCR fragment was subjected to sequence analysis [6].
• RT-PCR was conducted to determine ERalpha and ERbeta and glyceraldehyde-3-phosphate dehydrogenase mRNA abundance in four intrauterine tissues of the pregnant rhesus monkey [6].
• Western blot analysis using two anti-ERbeta antibodies specific for mammalian ERbeta sequences (PA1-310B and PA1-311) was employed to examine ERbeta protein expression in neural tissues from ovariectomized (OVX) cynomolgus macaques and CF-1 mice as well as to assess potential regulatory effects of acute and extended estradiol (E(2)) treatment [7].
• The marmoset monkey, therefore, provides a suitable animal model in which to investigate the impact of ERbeta variant expression on tissue responsiveness to oestrogens [5].
• Ovariectomized macaques (Macaca fascicularis) were used to study the regulation of ERalpha and ERbeta in the endometrium by immunohistochemistry and in situ hybridization after long-term hormone treatment [9].

References