ACTH and Phorbol Ester Stimulated Redistribution of Protein Kinase C in Human Cortisol-Producing Adrenal Adenoma

Abstract

We studied the steroidogenetic action and concomitant subcellular redistribution of protein kinase C (PKC) in cortisol hypersecreting adrenal adenoma cells obtained from two patients with Cushing's syndrome. Isolated adenoma cells were treated with 10−9M and 10−6M 12-O-tetradecanoyl phorbol-13-acetate (TPA) or 10−6M ACTH. Treatment of the isolated adenoma cells with TPA resulted in cortisol secretion equivalent to that with ACTH-treatment. Immunoblot analysis of PKC during treatment with ACTH or TPA showed that PKCβ translocated from cytosol to membrane. A small amount of PKCα, but not membrane-associated PKCα, was detectable in the cytosolic fraction. It appeared that TPA-induced cortisol secretion mimicked ACTH-induced cortisol secretion, and that PKCβ translocated from cytosol to membrane on stimulation by both ACTH and TPA. We suggested that ACTH-induced cortisol secretion in human cortisol hypersecreting adrenal adenoma is mediated by PKCβ activation. © 1994, The Japan Endocrine Society. All rights reserved.