HUMAN 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 AND TYPE-2 ISOENZYMES HAVE OPPOSITE ACTIVITIES IN CULTURED-CELLS AND CHARACTERISTIC CELL-SPECIFIC AND TISSUE-SPECIFIC EXPRESSION
Mm. Miettinen et al., HUMAN 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 AND TYPE-2 ISOENZYMES HAVE OPPOSITE ACTIVITIES IN CULTURED-CELLS AND CHARACTERISTIC CELL-SPECIFIC AND TISSUE-SPECIFIC EXPRESSION, Biochemical journal, 314, 1996, pp. 839-845
17 beta-Hydroxysteroid dehydrogenase (17HSD) isoenzymes catalyse the i
nterconversion 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 acti
vity and the expression of 17HSD type 1 and 2 isoenzymes in several hu
man cell types and tissues. The data indicate that in cultured cells t
he direction of 17HSD activity is exclusively determined by the expres
sion of these distinct isoenzymes. The intracellular environment could
not modulate the direction of the enzyme activities in any of the cel
l types analysed. 17HSD type 1 acts as a reductase converting oestrone
into oestradiol, whereas 17HSD type 2 possesses oxidative activity in
activating oestradiol by converting it into oestrone. The data, furthe
rmore, suggest that of the two 17HSD type 1 mRNAs (1.3 and 2.3 kb), ex
pression 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 i
n some target cells of sex steroid action. The opposite reaction direc
tions observed in the cultured cells, together with differences in the
distribution of the isoenzymes, suggest that type 1 is involved in oe
stradiol production in females while type 2 plays a role in the inacti
vation of this sex steroid in peripheral tissues, both in females and
in males. However, some examples exist of simultaneous expression of b
oth enzymes in the same cell type or tissue.