F. Jakob et al., EXPRESSION AND REGULATION OF AROMATASE AND 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-4 IN HUMAN THP-1 LEUKEMIA-CELLS, Journal of steroid biochemistry and molecular biology, 55(5-6), 1995, pp. 555-563
Estradiol is active in proliferation and differentiation of sex-relate
d tissues like ovary and breast. Glandular steroid metabolism was for
a long time believed to dominate the estrogenic milieu around any cell
of the organism. Recent reports verified the expression of estrogen r
eceptors in ''non-'target'' tissues as well as the extraglandular expr
ession of steroid metabolizing enzymes. Extraglandular steroid metabol
ism proved to be important in the brain, skin and in stromal cells of
hormone responsive tumors. Aromatase converts testosterone into estrad
iol and androstenedione into estrone, thereby activating estrogen prec
ursors. The group of 17 beta-hydroxysteroid dehydrogenases catalyzes t
he oxidation and/or reduction of the forementioned compounds, e.g. est
radiol/estrone, thereby either activating or inactivating estradiol. A
romatase is expressed and regulated in the human THP 1 myeloid leukemi
a cell line after vitamin D/GMCSF-propagated differentiation. Aromatas
e expression is stimulated by dexamethasone, phorbolesters and granulo
cyte/macrophage stimulating factor (GMCSF). Exons 1.2 and 1.4 are expr
essed in PMA-stimulated cells only, exon 1.3 in both PMA- and dexameth
asone-stimulated cells. Vitamin D-differentiated THP 1 cells produce a
net excess of estradiol in culture supernatants, if testosterone is g
iven as aromatase substrate. In contrast, the 17 beta-hydroxysteroid d
ehydrogenase type 4 (17 beta-HSD 4) is abundantly expressed in unstimu
lated THP 1 cells and is further stimulated by glucocorticoids (2-fold
). The expression is unchanged after vitamin D/GMCSF-propagated differ
entiation. 17 beta-HSD 4 expression is not altered by phorbolester tre
atment in undifferentiated cells but is abolished after vitamin D-prop
agated differentiation along with downregulation of beta-actin. Protei
n kinase C activation therefore appears to dissociate the expression o
f aromatase and 17 beta-HSD 4 in this differentiation stage along the
monocyte/phagocyte pathway of THP 1 myeloid cells. The expression of s
teroid metabolizing enzymes in myeloid cells is able to create a micro
environment which is uncoupled from dominating systemic estrogens. The
se findings may be relevant in the autocrine, paracrine or iuxtacrine
cellular crosstalk of myeloid cells in their respective states of term
inal differentiation, e.g. in bone metabolism and inflammation.