Formation and inactivation of testosterone is performed by various members of the 17 -hydroxysteroid dehydrogenase (17 -HSD) family. The main player in testosterone formation is considered to be 17 -HSD type 3, which catalyzes the reduction of androstenedione to testosterone with high efficiency and is almost exclusively expressed in testis. So far, only the mammalian homologs have been characterized but nothing is known about the role of 17 -HSD type 3 in other vertebrates. In this study, we describe the identification and characterization of the zebrafish homolog. We found zebrafish 17 -HSD type 3 to be expressed in embryogenesis from sphere to 84 h post-fertilization. Expression was also detected in various tissues of both male and female adults, but displayed sexual dimorphism. Interestingly, expression was not highest in male testis but in male liver. In female adults, strongest expression was observed in ovaries. At the subcellular level, both human and zebrafish 17 -HSD type 3 localize to the endoplasmic reticulum. The zebrafish enzyme in vitro effectively catalyzed the conversion of androstenedione to testosterone by use of NADPH as cofactor. Among further tested androgens epiandrosterone and dehydroepiandrosterone were accepted as substrates and reduced at C-17 by the human and the zebrafish enzyme. Androsterone and androstanedione though, were only substrates of human 17 -HSD type 3, not the zebrafish enzyme. Furthermore, we found that both enzymes can reduce 11-ketoandrostenedione as well as 11 -hydroxyandrostenedione at C-17 to the respective testosterone forms. Our results suggest that 17 -HSD type 3 might play slightly different roles in zebrafish compared with human although testosterone itself is likely to have similar functions in both organisms.
This article is available online at http://www.jlr.org Fatty acids are among other metabolites essential components of the human metabolome. In cells, phospholipids containing highly unsaturated fatty acids (HUFAs) such as arachidonic acid (all-cis -5,8,11,14-eicosatetraenoic acid or C20:4n-6) and docosahexaenoic acid [22:6( -3), all-cis -docosa-4,7,10,13,16,19-hexaenoic acid or C22:6n-3] have a positive effect on the fl uidity of cell membranes. On the molecular level, HUFAs fulfi ll several other central functions like acting as second messengers in intracellular signaling pathways or regulating transcription. On the physiological level, HUFAs are important for brain development, acquisition of cognitive behaviors, and development of visual functions in early life. In addition, HUFAs are precursors for eicosanoids (leukotriens and prostaglandins), which play an important role in infl ammatory processes ( 1 ).The production of HUFAs from dietary fatty acids includes several desaturation and elongation steps. The desaturases involved in this reaction cascade, delta-6 desaturase and delta-5 desaturase, are the rate-limiting enzymes. Both are expressed in the majority of human tissues, with highest levels in liver and to a smaller amount in brain, heart, and lung ( 2, 3 ). Delta-6 desaturase inserts a double bond at position 6 and after an elongation step, delta-5 desaturase inserts an additional double bond at
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