Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. Distinct profiles predict the essential thrombocythemic phenotype.
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 17beta-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 17beta-HSD3 activity corresponding to approximately 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 17beta-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.
Gnatenko
Dmitri V
DV
Department of Medicine, State University of New York at Stony Brook, New York 11794-8151, USA.
Cupit
Lisa D
LD
Huang
Emily C
EC
Dhundale
Anilkumar
A
Perrotta
Peter L
PL
Bahou
Wadie F
WF
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism; D013922:Thrombocytosis / Q000097:blood* / Q000201:enzymology / Q000473:pathology*; D013997:Time Factors; D015854:Up-Regulation
D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase