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Thromb Haemost 2005; 94(02): 412-421
DOI: 10.1160/TH05-01-0037
Platelets and Blood Cells
Schattauer GmbH

Platelets express steroidogenic 17β–hydroxysteroid dehydrogenases

Distinct profiles predict the essential thrombocythemic phenotype
Dmitri V. Gnatenko
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
,
Lisa D. Cupit
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
,
Emily C. Huang
2   Center for Biotechnology and Department of Bioengineering, State University of New York, Stony Brook, New York, USA
,
Anilkumar Dhundale
2   Center for Biotechnology and Department of Bioengineering, State University of New York, Stony Brook, New York, USA
,
L. Perrotta Peter
3   Department of Pathology, State University of New York at Stony Brook, New York, USA
,
Wadie F. Bahou
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
4   Program in Genetics, State University of New York at Stony Brook, New York, USA
› InstitutsangabenFinancial support: This work was supported by grants HL49141, HL76457, HL04239, the American Heart Association, the Department of Defense Myeloproliferative Disorders Research Program, a Stony Brook Targeted Research Award, and NIH Center grant MO1 10710-5 to the University Hospital General Clinical Research Center.
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Publikationsverlauf

Received: 18. Januar 2005

Accepted after major revision: 29. Mai 2005

Publikationsdatum:
05. Dezember 2017 (online)

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Summary

Human blood platelets have important, regulatory functions in diverse hemostatic and pathological disorders, including vascular remodeling, inflammation, and wound repair. Microarray analysis was used to study the molecular basis of essential thrombocythemia, a myeloproliferative disorder with quantitative and qualitative platelet defects associated with cardiovascular and thrombohemorrhagic symptoms, not infrequently neurological. A platelet-expressed gene (HSD17B3) encoding type 3 17β-hydroxysteroid dehydrogenase (previously characterized as a testis-specific enzyme catalyzing the final step in gonadal synthesis of testosterone) was selectively down-regulated in ET platelets, with reciprocal induction of the type 12 enzyme (HSD17B12). Functional 17β-HSD3 activity corresponding to ∼10% of that found in murine testis was demonstrated in normal platelets. The induction of HSD17B12 in ET platelets was unassociated with a concomitant increase in androgen biosynthesis, suggesting distinct functions and/or substrate specificities of the types 3 and 12 enzymes. Application of a molecular assay distinguished ET from normal platelets in 20 consecutive patients (p < 0.0001). These data provide the first evidence that distinct subtypes of steroidogenic 17β−HSDs are functionally present in human blood platelets, and that the expression patterns of HSD17B3 and HSD17B12 are associated with an uncommon platelet disorder manifest by quantitative and qualitative platelet defects.

Keywords

Platelets - hydroxysteroid dehydrogenases - microarray - essential thrombocythemia
 

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