Hormone-sensitive cholesterol ester hydrolase in adrenal tumor cells: activation by corticotropin and tetradecanoyl phorbol acetate.
The effects of corticotropin (ACTH) and tetradecanoyl phorbol acetate (TPA) on cholesterol ester hydrolase, intracellular cholesteryl ester concentration and steroid hormone formation were studied in mouse adrenal tumor cells (Y-1) in monolayer culture. Cholesterol ester hydrolase activity increased about 2-fold during 7 min incubation with ACTH, dibutyryl 3',5'-cyclic AMP (dbcAMP) and TPA at maximally effective concentrations; whereas, incubation with phorbol monoacetate had no effect. Long-term exposure to ACTH and dbcAMP markedly lowered intracellular cholesteryl [3H]-oleate concentration and highly increased steroid hormone output, while TPA treatment resulted in lowering cholesteryl [3H]-oleate content without affecting steroid hormone formation. Calcium activated phospholipid-dependent protein kinase C was detected in Y-1 cell cytosol. It is concluded that the mouse adrenal tumor cells in monolayer culture respond to ACTH in a fashion similar to normal adrenocortical cells; whereas, the response to the phorbol ester TPA (possibly mediated through protein kinase C) involves activation of cholesterol ester hydrolase and cholesteryl ester depletion, however, without affecting steroid hormone secretion.
Balkow
C
C
Institut fur Physiologische Chemie, Ruhr Universitat, Bochum, Federal Republic of Germany.
Trzeciak
W H
WH
Kunau
W H
WH
D000302:Adrenal Cortex / Q000201:enzymology*; D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007700:Kinetics; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D002787:Sterol Esterase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002788:Cholesterol Esters; C014409:cholesteryl oleate; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase; D013755:Tetradecanoylphorbol Acetate