ACTH and phorbol ester stimulated redistribution of protein kinase C in human cortisol-producing adrenal adenoma.
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(-9) M and 10(-6) M 12-O-tetradecanoyl phorbol-13-acetate (TPA) or 10(-6) M 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 PKC beta translocated from cytosol to membrane. A small amount of PKC alpha, but not membrane-associated PKC alpha, was detectable in the cytosolic fraction. It appeared that TPA-induced cortisol secretion mimicked ACTH-induced cortisol secretion, and that PKC beta 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 PKC beta activation.
Kajita
K
K
Nagahama Red Cross Hospital, Shiga, Japan.
Ishizuka
T
T
Yamamoto
M
M
Nagashima
T
T
Taniguchi
O
O
Mune
T
T
Murayama
M
M
Kitagawa
S
S
Yasuda
K
K
D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D015151:Immunoblotting; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone