The effects of estradiol on 17β-hydroxysteroid dehydrogenase type IV and androgen receptor expression in the developing zebra finch song system

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, and, third, if so does E2 modulate co-expression? Female finches implanted with 50μg 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.

Genome–brain–behavior interdependencies as a framework to understand hormone effects on learned behavior

“…3) (London et al, 2003(London et al, , 2006London and Clayton, 2010;Thompson et al, 2011;Tomaszycki et al, 2009). This is consistent with the potential for neurosteroids to signal during song learning and adult singing.…”

“…The bulk of transcriptional regulation would then appear to occur through androgen receptor binding. Interestingly, some of the clearest evidence for steroid regulation of downstream transcription comes from studies that demonstrate steroids regulate expression of other steroid-related genes (Kim et al, 2004;Nordeen et al, 1986;Thompson et al, 2011). Steroid-receptor binding and receptor-genome binding are areas where more work needs to be done.…”

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

“…It converts the more active hormone, estradiol, to the less active estrone. Sex differences in HSD17B4 expression with estradiol supplementation have been noted in zebra fish [64]. In addition, the position of our lead marker at a predicted transcription factor binding site located just upstream of a putative protein coding splice variant of HSD17B4 indicates a potential function for the association signal observed at this locus and may warrant additional follow-up work.…”

Sex differences and rapid estrogen signaling: A look at songbird audition

“…The major portion of sexual differentiation in young zebra finches occurs during the incubation and post-hatching periods, which has allowed particular accessibility to manipulations during critical windows of differentiation and song learning. Treatment with E2 in the first two weeks of hatching is a potent manipulation that can masculinize female hatchlings via organizational actions, leading to females that are able to sing in adulthood (Adkins-Regan et al , 1994, Grisham et al , 2008, Gurney & Konishi, 1980, Konishi & Akutagawa, 1988, Nordeen et al , 1986, Thompson et al , 2011). …”