Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch

Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
BMC Neuroscience (Impact Factor: 2.67). 04/2010; 11(1):46. DOI: 10.1186/1471-2202-11-46
Source: PubMed


Steroids are small molecule hormones derived from cholesterol. Steroids affect many tissues, including the brain. In the zebra finch, estrogenic steroids are particularly interesting because they masculinize the neural circuit that controls singing and their synthesis in the brain is modulated by experience. Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors. Based on these analyses, we also investigated neural expression of a cholesterol transport protein gene in the context of song neurobiology.
We present sequence-based analysis of twenty steroid-related genes using the genome assembly and other resources. Generally, zebra finch genes showed high homology to genes in other species. The diversity of steroidogenic enzymes and receptors may be lower in songbirds than in mammals; we were unable to identify all known mammalian isoforms of the 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase families in the zebra finch genome assembly, and not all splice sites described in mammals were identified in the corresponding zebra finch genes. We did identify two factors, Nobox and NR1H2-RXR, that may be important for coordinated transcription of multiple steroid-related genes. We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR). We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed. Also, transcription of TSPO, but not StAR, may be regulated by the experience of hearing song.
The genes required for estradiol synthesis and action are represented in the zebra finch genome assembly, though the complement of steroidogenic genes may be smaller in birds than in mammals. Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated. Integration of genomic and neuroanatomical analyses will continue to provide insights into the evolution and function of steroidogenesis in the songbird brain.

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    • "Major enzyme types from two gene families (Abe et al., 2012), 3b- and 17b-hydroxysteroid dehydrogenase, are confirmed in zebra finch brain biochemically (Cam and Schlinger, 1998; London et al., 2010; Soma et al., 2004; Tam and Schlinger, 2007; Vanson et al., 1996). Examination of the genome, however, suggests that several members of both families that are present and active in mammals are absent in birds (London and Clayton, 2010). Within the subset of genes identified in the zebra finch genome, those experimentally confirmed in the zebra finch brain are among those highly conserved across clade. "
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    ABSTRACT: Genome technologies are transforming all areas of biology, including the study of hormones, brain and behaviour. For birds, annotated reference genome assemblies are rapidly being produced for many avian species. Here we briefly review the basic concepts and tools used in genomics. We then consider how these are informing the study of avian behavioural neuroendocrinology, focusing in particular on lessons from the study of songbirds. We discuss the impact of having a complete "parts list" for an organism; the transformational potential of studying large sets of genes at once instead one gene at a time; the growing recognition that environmental and behavioural signals trigger massive shifts in gene expression in the brain; and the prospects for using comparative genomics to uncover the genetic roots of behavioural variation. Throughout, we identify promising new directions for bolstering the application of genomic information to further advance the study of avian brain and behaviour.
    Frontiers in Neuroendocrinology 10/2013; 35(1). DOI:10.1016/j.yfrne.2013.09.004 · 7.04 Impact Factor
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    • "At day 25 posthatching , this gene is expressed in 3 song regions: LMAN, Area X and HVC (Tomaszycki, et al., 2009). Expression is higher in the male zebra finch LMAN as early as day 5 (London et al., 2010) and is significantly increased in males than in females in HVC at post hatch day 25 (Tomaszycki, et al., 2009). This study asks three primary questions: First, how does E2 treatment affect HSD17B4 mRNA expression in day 25 males and females? "
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    ABSTRACT: Recent work in zebra finches suggests that genes and hormones may act together to masculinize the brain. This study tested the effects of exogenous estradiol (E2) on 17β-hydroxysteroid dehydrogenase type IV (HSD17B4) and the co-localization of HSD17B4 and androgen receptor (AR) mRNA. We asked three primary questions: First, how does post-hatching E2 treatment affect HSD17B4 mRNA expression in males and females? Second, is this gene expressed in the same cells as AR. Third, if so does E2 modulate co-expression? Female finches implanted with 50 μg of E2 on the third day post-hatching showed a significant increase in the density of cells expressing HSD17B4 and AR in HVC at day 25. Co-localization of AR cells that also expressed HSD17B4 was high across groups (>81%). We found significant sex differences in co-localization in both the HVC and Area X of control animals, with males showing a higher percentage of cells expressing AR mRNA that also expressed HSD17B4 in comparison to females. However, although E2 treatments significantly increased the number of cells expressing HSD17B4 mRNA and AR mRNA in the HVC of females, the percentage of HSD17B4 cells co-expressing AR was reduced in HVC and Area X in E2-treated animals. These results lend support to the hypothesis that genes and hormones may act in concert to modulate the sexually differentiation of the zebra finch song system. Further, the data suggest that a single hormonal mechanism cannot mimic the complex development of male singing behavior and associated song nuclei.
    Brain research 07/2011; 1401:66-73. DOI:10.1016/j.brainres.2011.05.031 · 2.84 Impact Factor
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    ABSTRACT: An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena. See research articles,, and
    Journal of Biology 04/2010; 9(3):19. DOI:10.1186/jbiol222
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