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.
Highlights
Aromatase cytochrome P450arom is the only enzyme performing the conversion of androgens into estrogens (Lephart, 1996; Garcia-Segura et al, 2003)
The expression of aromatase B in the teleost brain is exclusive to one particular cell type, the radial glial cell (RGC) (Forlano et al, 2001; Diotel et al, 2010; Xing et al, 2014), which allows direct in vivo study of glial aromatase contributions without interference from neuronal compartments
All these lines of evidence suggest that both RGC progenitor and steroidogenic functions contribute to neurogenesis in adult vertebrate brains
Summary
Aromatase cytochrome P450arom (cyp19) is the only enzyme performing the conversion of androgens into estrogens (Lephart, 1996; Garcia-Segura et al, 2003). In all species of vertebrates, including mammals, birds, and teleost fish, aromatase expression can be found in the brain in addition to testes and ovaries (Balthazart and Ball, 1998; Forlano et al, 2001). It is very difficult to compare aromatase activity among species, it is clear that activity in the forebrain of teleost fish is much higher (100–1000 times) than in birds and mammals All these data indicate that teleost fish are excellent models to study function and regulation of glial aromatase. Recent studies indicate that RGCs are the progenitors of both neurons and glia during development, and are the source of new neurons in adult vertebrate brains (AlvarezBuylla et al, 2001; Zupanc and Clint, 2003; Pellegrini et al, 2007). All these lines of evidence suggest that both RGC progenitor and steroidogenic functions contribute to neurogenesis in adult vertebrate brains
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