Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4
1 Interdepartmental Program in Neuroscience, University of California at Los Angeles, Los Angeles, CA, USA
2 Department of Physiological Science, University of California at Los Angeles, Los Angeles, CA, USA
3 Laboratory of Neuroendocrinology of the Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA
4 Department of Ecology and Evolutionary Biology, University of California at Los Angeles, Los Angeles, CA, USA
5 Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Citation and License
BMC Neuroscience 2010, 11:47 doi:10.1186/1471-2202-11-47Published: 1 April 2010
Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2) is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4), an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ) and females (ZW) because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females.
Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain.
Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.