Factors affecting the conversion of androstenedione to estrogens by human fetal hepatocytes in monolayer culture.
The purpose of the present investigation was to characterize and determine what hormones affect the activity of aromatase in human fetal hepatocytes maintained in primary monolayer culture. The major product of aromatization of androstenedione was estrone sulfate. Optimal conditions for assay of aromatase activity in fetal liver cells were determined. The apparent Km for androstenedione was 50 nM. Aromatase activity was stimulated by glucocorticoids in the presence of fetal calf serum. The concentration of dexamethasone required for half-maximal stimulation was 10(-8) M, similar to the concentration required for half-maximal binding to glucocorticoid receptors. This action of dexamethasone was inhibited by cortisol 21-mesylate, a glucocorticoid antagonist. Aromatase activity was also stimulated by (Bu)2cAMP and cholera toxin, and was inhibited by fetal calf serum. This effect of fetal calf serum was mimicked by epidermal growth factor. However, epidermal growth factor did not mimic the permissive action of serum to stimulate aromatase activity by dexamethasone. In these respects, the regulation of aromatase activity of human fetal hepatocytes is similar to that of human adipose stromal cells. A polycyclic hydrocarbon, benzo(a)pyrene, which causes induction of aryl hydrocarbon hydroxylase activity in fetal hepatocytes, inhibited the stimulation of aromatase activity by dexamethasone. Of a number of hormones tested, including glucagon, insulin, angiotensin II, ACTH, hCG, GH, PRL, and T3, only glucocorticoids were effective in stimulating aromatase activity of human fetal hepatocytes. These results emphasize the complex and multiparameter nature of the regulation of aromatase activity in this as in other tissues.
Lanoux
M J
MJ
Cleland
W H
WH
Mendelson
C R
CR
Carr
B R
BR
Simpson
E R
ER
D000735:Androstenedione / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000031:analogs & derivatives / Q000096:biosynthesis; D005312:Fetal Blood; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*
D004967:Estrogens; D004970:Estrone; D000735:Androstenedione; D004815:Epidermal Growth Factor; D003994:Bucladesine; C027504:cortisol 21-mesylate; D003907:Dexamethasone; D010088:Oxidoreductases; D001141:Aromatase; C017296:estrone sulfate; D006854:Hydrocortisone