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.