Human 17 beta-hydroxysteroid dehydrogenase type 1 and type 2 isoenzymes have opposite activities in cultured cells and characteristic cell- and tissue-specific expression.
17 beta-Hydroxysteroid dehydrogenase (17HSD) isoenzymes catalyse the interconversion between highly active 17 beta-hydroxy- and low-activity 17-keto-steroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize 17HSD activity and the expression of 17HSD type 1 and 2 isoenzymes in several human cell types and tissues. The data indicate that in cultured cells the direction of 17HSD activity is exclusively determined by the expression of these distinct isoenzymes. The intracellular environment could not modulate the direction of the enzyme activities in any of the cell types analysed. 17HSD type 1 acts as a reductase converting oestrone into oestradiol, whereas 17HSD type 2 possesses oxidative activity inactivating oestradiol by converting it into oestrone. The data, furthermore, suggest that of the two 17HSD type 1 mRNAs (1.3 and 2.3 kb), expression of the 1.3 kb mRNA is related to enzyme concentration in all the cell types studied. This mRNA is principally expressed in cells of placental and ovarian origin, but is also present in malignant breast epithelial cells. In contrast, 17HSD type 2 is more widely expressed. It is present in several oestradiol-metabolizing tissues as well as in some target cells of sex steroid action. The opposite reaction directions observed in the cultured cells, together with differences in the distribution of the isoenzymes, suggest that type 1 is involved in oestradiol production in females while type 2 plays a role in the inactivation of this sex steroid in peripheral tissues, both in females and in males. However, some examples exist of simultaneous expression of both enzymes in the same cell type or tissue.
Miettinen
M M
MM
Biocenter Oulu and Department of Clinical Chemistry, University of Oulu, Finland.
Mustonen
M V
MV
Poutanen
M H
MH
Isomaa
V V
VV
Vihko
R K
RK
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002522:Chlorocebus aethiops; D016889:Endometrial Neoplasms; D004717:Endometrium / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D008297:Male; D010051:Ovarian Neoplasms; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases