Direct Regulation of Aromatase B Expression by 17β-Estradiol and Dopamine D1 Receptor Agonist in Adult Radial Glial Cells

Abstract

Aromatase cytochrome P450arom (cyp19) is the only enzyme that has the ability to convert androgens into estrogens. Estrogens, which are produced locally in the vertebrate brain play many fundamental roles in neuroendocrine functions, reproductive functions, socio-sexual behaviors, and neurogenesis. Radial glial cells (RGCs) are neuronal progenitor cells that are abundant in fish brains and are the exclusive site of aromatase B expression and neuroestrogen synthesis. Using a novel in vitro RGC culture preparation we studied the regulation of aromatase B by 17β-estradiol (E2) and dopamine (DA). We have established that activation of the dopamine D1 receptor (D1R) by SKF 38393 up-regulates aromatase B gene expression most likely through the phosphorylation of cyclic AMP response element binding protein (CREB). This up-regulation can be enhanced by low concentration of E2 (100 nM) through increasing the expression of D1R and the level of p-CREB protein. However, a high concentration of E2 (1 μM) and D1R agonist together failed to up-regulate aromatase B, potentially due to attenuation of esr2b expression and p-CREB levels. Furthermore, we found the up-regulation of aromatase B by E2 and DA both requires the involvement of esr1 and esr2a. The combined effect of E2 and DA agonist indicates that aromatase B in the adult teleost brain is under tight control by both steroids and neurotransmitters to precisely regulate neuroestrogen levels.

Effects of bifenthrin exposure on the estrogenic and dopaminergic pathways in zebrafish embryos and juveniles

“…Dopamine can block synthesis and release of GnRH , modulating gonadotropin levels by increasing and decreasing them according to receptor subtype , which will lead to decreased levels of E2. Furthermore, dopamine can also control E2 levels by regulating brain aromatase, an enzyme that converts androgens to estrogens . Xing et al showed that a dopaminergic agonist was able to regulate aromatase B by increasing or decreasing its expression, which is potentially different from the inhibition effect dopamine exerts over GnRH.…”

Temporal patterns of induction and recovery of biomarker transcriptional responses to 4‐Nonylphenol and 17β‐estradiol in the estuarine arrow goby, Clevelandia ios

“…For instance, waterborne 4‐NP and E2 exposures for up to six days had no effect on brain esr1 mRNA abundance in rainbow trout fry (Vetillard and Bailhache, ). In one recent study by Xing and coworkers () using cultured radial glial cells from goldfish, E2 was observed to upregulate the abundance of transcripts encoding both cyp19a1b and esr2b , but not esr1 or esr2a . In this same study, this E2 effect on cyp19a1b mRNAs was also linked to E2‐induced recruitment of the dopamine D1 receptor and the level of phosphorylated cyclic AMP response element binding protein (p‐CREB).…”

“…In this same study, this E2 effect on cyp19a1b mRNAs was also linked to E2‐induced recruitment of the dopamine D1 receptor and the level of phosphorylated cyclic AMP response element binding protein (p‐CREB). Xing and colleagues () suggested, however, that this synergistic interaction between E2 and dopamine pathways in upregulating cyp19a1b is not solely mediated by esr2b , but also requires involvement of endogenous esr1 and esr2a expression. While future studies are needed to explore these interactions between aromatase, E2, and dopamine pathways in the brain more fully, the inconsistent and variable responses of ER transcriptional expression to E2 in teleost fishes indicate that esr genes have limited utility as biomarkers for xenoestrogen exposure.…”

Neuroendocrine disruption of organizational and activational hormone programming in poikilothermic vertebrates

“…These pathways may be involved in organizational effects in fish if new neurons are generated in response to the steroids or possibly also in activational effects in fish (Xing et al 2014; 2015; 016). Recently, Xing et al (2015) demonstrated that E2 concentrations in the 100 nM range plus activation of the dopamine D1 receptor (D1R) with a specific dopamine agonist up-regulated brain aromatase in RGCs. At higher concentrations (1 μM E2), this effect was inhibited.…”

“…In the model proposed to explain these results, it is clear that D1R functions through cAMP signaling to phosphorylate cAMP Responsive Element Binding Protein (CREB), which then acts in concert with the ER to upregulate brain aromatase. This dopaminergic regulation of RGC is thus modulated by E2 (Xing et al 2015). …”