Oestrogen formation from C19 precursors in human choriocarcinoma in culture.
A cloned cell line of human choriocarcinoma was evaluated as a model of human placental oestrogen production. Oestrone formation from dehydroepiandrosterone (D), D-sulphate (DS) or 4-androstenedione (A) was less than or equal to 5% of oestradiol-17beta (Oe2) formation. Oe2 formation from D and A was similar (100-150 pmole/h/10(7) cells); that from DS was 10 times less. Omitting serum from the medium increased Oe2 yield from DS 4-fold; addition of albumin restored these yields to control values (P greater than 0.05, t-test), presumably by binding DS. N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphoric acid and theophylline treatment for 72 h stimulated (P less than 0.01) Oe2 formation from D (36%), DS (66%) and A (183%). In intact cells, sulphatase activity, Oe2 formation from D and Oe2 formation from DS equalled those in homogenates (P greater than 0.05) but Oe2 formation from D was greater than that from DS in both systems (P less than 0.001), indicating a deficiency of sulphatase relative to subsequent enzymes of oestrogen synthesis. Steroids, at concentrations previously shown to inhibit placental sulphatase or 3beta-hydroxysteroid dehydrogenase, did not inhibit choriocarcinoma enzymes. Except for its relative sulphatase deficiency and insusceptibility of oestrogen synthesizing enzymes to steroid inhibitors, choriocarcinoma appears to be a useful model of placental oestrogen synthesis.
D000523:Algestone / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000735:Androstenedione / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000494:pharmacology; D002822:Choriocarcinoma / Q000201:enzymology / Q000378:metabolism*; D002999:Clone Cells / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology; D066298:In Vitro Techniques; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D013429:Sulfatases / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014594:Uterine Neoplasms / Q000378:metabolism*
D000728:Androgens; D006908:Hydroxyprogesterones; D011498:Protein Precursors; D000523:Algestone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D003994:Bucladesine; D002784:Cholesterol; D013806:Theophylline; D013429:Sulfatases