Distinct Roles of Estrogen Receptors in the Regulation of Vitellogenin Expression in Orange-Spotted Grouper (Epinephelus coioides)

Abstract

During their breeding season, estrogen induces vitellogenin (VTG) production in the liver of teleost fish through estrogen receptors (ERs) that support oocyte vitellogenesis. There are at least three ER subtypes in teleost fish, but their roles in mediating E2-induced VTG expression have yet to be ascertained. In this study, we investigated the expression of vtgs and ers in the liver of orange-spotted groupers (Epinephelus coioides). Their expression levels were significantly increased in the breeding season and were upregulated by an estradiol (E2) injection in female fish, except for the expression of erβ1. The upregulation of vtgs, erα and erβ2 by E2 was also observed in primary hepatocytes, but these stimulatory effects could be abolished by ER antagonist ICI182780 treatment. Subsequent studies showed that ERβ antagonist Cyclofenil downregulated the E2-induced expression of vtg, erα, and erβ2, while the ERβ agonist DPN simulated their expression. Knockdown of erβ2 by siRNA further confirmed that ERβ2 mediated the E2-induced expression of vtgs and erα. To reveal the mechanism of ERβ2 in the regulation of erα expression, the erα promoter was cloned, and its activity was examined in cells. E2 treatment simulated the activity of the erα promoter in the presence of ERβ2. Deletions and site-directed mutations showed that the E2 up-regulated transcriptional activity of erα occurs through a classical half-estrogen response element- (ERE) dependent pathway. This study reveals the roles of ER subtypes in VTG expression in orange-spotted groupers and provides a possible explanation for the rapid and efficient VTG production in this species during the breeding season.

Genome-Wide Identification, Expression and Response to Estrogen of Vitellogenin Gene Family in Sichuan Bream (Sinibrama taeniatus)

“…The research conducted on zebrafish embryos demonstrated that the specific knockdown of erβs using morpholinos effectively suppressed the estradiol-induced expression of vtg and erα mRNA [ 71 ]. However, more studies have suggested that ERα predominantly mediates estrogenic effects in fish Vtg synthesis [ 29 , 30 , 72 ]. ERα expression in the liver increases during the breeding season, which parallels the trend of E 2 and Vtg levels in the blood [ 73 , 74 ].…”

Interaction of Bisphenol A and Its Analogs with Estrogen and Androgen Receptor from Atlantic Cod (Gadus morhua)

“…This discrepancy may point to a possible role of hepatic biotransformation enzymes in converting this compound into a metabolite that is a favorable agonist of the gmEra receptor. − This has previously been shown for the Era antagonist tamoxifen, which in some mammalian species can be metabolized into 4-hydroxytamoxifen that further lose its alkylaminoethane side chain to form the estrogenic compounds metabolite E or tamoxifen bisphenol . However, it cannot be ruled out that BPG rather interact with and activate Erb subtypes or membrane-bound estrogen receptors (GPER) in cod liver slices, which previously have been demonstrated to be able to influence Vtg synthesis in other teleosts. − Notably, BADGE was the only BPA analog that demonstrated antiestrogenic effects in the ex vivo assay by significantly reducing the amount of Vtg levels in the PCLS media. This is interesting, as BADGE did not antagonize EE2-mediated gmEra activity in the luciferase reporter gene assay.…”

Season affects the estrogen system and the immune response of common carp

“…Similar to our observation for carp, the constitutive expression of these genes in rainbow trout was higher in the course of autumn (October–November) than in the spring. Also, compared to the breeding females (sampled in April), non-breeding females of the orange-spotted grouper (sampled in February) had lower expression of vtg , erα , erβ1 and erβ2 in the liver (Ye et al 2022 ).…”

“…In turn, in rainbow trout, a higher level of E2 was reported in May and in September (Chen et al 2021 ). In addition, high E2 concentrations affect the level of vitellogenin, as well as the expression of estrogen receptors and aromatase (Nelson et al 2007 ; Nagler et al 2012 ; Ye et al 2022 ).…”