AI Article Synopsis
- The study focuses on mouse type 5 17beta-Hydroxysteroid dehydrogenase (17beta-HSD), a crucial enzyme for regulating sex steroid levels, which is part of the aldo-keto reductase superfamily, unlike other 17beta-HSD types that belong to the short-chain alcohol dehydrogenase family.
- The gene consists of 16 kb with 9 exons and 8 introns, and is primarily expressed in the liver with lower levels in the kidney; significant transcription activity was identified near the initiation codon.
- The enzyme predominantly converts 4-androstenedione and androstanedione into testosterone and dihydrotestosterone, respectively, and does so at a much higher
Article Abstract
17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) play a crucial role in the control of active sex steroid intracellular levels. Seven types of 17beta-HSD have been described. In this study, we report the cloning and characterization of the mouse type 5 17beta-HSD belonging to the aldo-keto reductase superfamily, in contrast with types 1, 2, 3, 4, 6, and 7 17beta-HSD which belong to the short-chain alcohol dehydrogenase family. The gene spans 16 kb and contains 9 exons separated by 8 introns. Primer extension analysis identified a major transcription start site beginning 50 nucleotides upstream from the ATG initiation codon. Northern blot analysis showed a high mRNA expression level in the liver and a weaker signal in the kidney. To determine more precisely the substrate specificity of the enzyme, we established a stable cell line expressing mouse type 5 17beta-HSD in transformed human embryonic kidney (293) cells. The transfected cell line preferentially catalyzes the transformation of 4-androstenedione (4-dione) and androstanedione (A-dione) into testosterone (T) and dihydrotestosterone (DHT), respectively. This data is somewhat in contradiction with a previous study that described the enzyme as estradiol 17beta-dehydrogenase. Our results indicate that the rate of transformation of estradiol (E(2)) to estrone (E(1)) represents only 1% of the rate of transformation of 4-dione to T. Mouse type 5 17beta-HSD shares 76% amino acid sequence identity with human type 5 17beta-HSD; 71%, 76%, 76% with rat 3alpha-HSD and human types 1 and 3 3alpha-HSDs, respectively; and 71%, 69% and 77% with mouse, rat and human 20alpha-HSD, respectively.
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| http://dx.doi.org/10.1016/s0167-4781(99)00106-2 | DOI Listing |
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