Interdisciplinary Centre for Marine and Environmental Research, CIMAR Associate Laboratory, University of Porto, Porto, Portugal.
J Steroid Biochem Mol Biol. 2013 Mar;134:8-14. doi: 10.1016/j.jsbmb.2012.10.005. Epub 2012 Oct 13.
HSD17B12 is a member of the hydroxysteroid dehydrogenase superfamily, a multifunctional group of enzymes involved in the metabolism of steroids, retinoids, bile and fatty acids. Whether the main role of HSD17B12 in mammals is in steroid or fatty acid metabolism is a subject of intense debate. In mollusks it has been shown that an HSD17B12 orthologue can convert estrone into estradiol in vitro, although its primary in vivo function remains unknown. To gain insight into its role in gastropods, we provide here the first cloning of Hsd17b12 in Nucella lapillus and its detailed tissue distribution through quantitative PCR. Furthermore, given that the endocrine disruptor tributyltin (TBT) has been reported to unbalance steroid and lipid levels in gastropods, we tested its impact in on NlHsd17b12 transcript expression. Our results show that NlHsd17b12 is ubiquitously expressed in all tissues analyzed, with higher levels in organs with high metabolic rates, such as kidney and digestive gland, a pattern consistent with an involvement in lipid metabolism. Exposure to TBT chloride at 100 ng Sn/L caused a decrease in NlHsd17b12 mRNA levels in digestive gland, after one and two months, while no effect was observed in gonads. Overall, these results suggest that in mollusks, as in mammals, this enzyme is likely to be involved in lipid metabolism, and emphasize the need to perform more detailed studies on its in vivo function, in order to understand its physiological role and the biological impact of its disruption by pollutants such as TBT.
HSD17B12 是羟甾类脱氢酶超家族的成员,该酶超家族是一组多功能酶,参与类固醇、视黄醇、胆汁酸和脂肪酸的代谢。HSD17B12 在哺乳动物中的主要作用是在类固醇还是脂肪酸代谢中,这是一个激烈争论的问题。在软体动物中,已经表明 HSD17B12 同源物可以在体外将雌酮转化为雌二醇,尽管其主要的体内功能仍然未知。为了深入了解其在腹足类动物中的作用,我们在这里首次克隆了 Nucella lapillus 中的 Hsd17b12,并通过定量 PCR 详细研究了其组织分布。此外,由于内分泌干扰物三丁基锡(TBT)已被报道会使腹足类动物的类固醇和脂质水平失衡,我们测试了它对 NlHsd17b12 转录表达的影响。我们的结果表明,NlHsd17b12 在所有分析的组织中广泛表达,在代谢率高的器官(如肾脏和消化腺)中表达水平更高,这一模式与参与脂质代谢一致。在 100ngSn/L 的 TBT 氯化物暴露下,消化腺中的 NlHsd17b12 mRNA 水平在一个月和两个月后下降,而在性腺中则没有观察到这种影响。总的来说,这些结果表明,在软体动物中,与哺乳动物一样,这种酶可能参与脂质代谢,并强调需要对其体内功能进行更详细的研究,以了解其生理作用以及污染物如 TBT 对其破坏的生物学影响。