Okadaic acid interferes with lipoprotein-supported corticosterone production in adrenal cells.
Rat adrenocortical cells in culture respond to stimulation by ACTH alone (15 fold over basal) and to ACTH + added lipoproteins (as an exogeneous source of cholesterol), with an additional 25-30 fold rise in steroidogenesis. With the addition of okadaic acid (OKA, 100 nM), a potent protein phosphatase inhibitor, the lipoprotein-induced rise in steroidogenesis is blocked. If 20 alpha-hydroxycholesterol is provided instead of lipoprotein-cholesterol, OKA has no effect suggesting that OKA affects only actively transported cholesterol. Since the OKA block is preceded by specific morphological changes in the cell (i.e., the loss of Golgi-associated microtubules followed by the disruption of the Golgi apparatus itself), it is hypothesized that some OKA-sensitive phosphoprotein associated with the microtubule/Golgi network of adrenocortical cells is critical for lipoprotein-derived cholesterol uptake and/or transport during steroidogenesis.
Azhar
S
S
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Palo Alto, California 94304.
Wang
H
H
Tsai
L
L
Reaven
E
E
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000096:biosynthesis*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006888:Hydroxycholesterols / Q000494:pharmacology; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D004988:Ethers, Cyclic; D006888:Hydroxycholesterols; D008074:Lipoproteins; D019319:Okadaic Acid; C025813:20-hydroxycholesterol; D000324:Adrenocorticotropic Hormone; D010749:Phosphoprotein Phosphatases; D003345:Corticosterone