Phospholipid/Calcium-Dependent Protein Kinase Activity in Human Cortisol-Hypersecreting Adrenocortical Adenoma

Ishizuka, Tatsuo; Murase, Hiroshi; Yasue, Midori; Miura, Kiyoshi; Nagao, Seiji; Nozawa, Yoshinori

doi:10.3164/jcbn.2.171

Cited by 2 publications

(1 citation statement)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the opposite translocation (membrane to cytosol) has been noted in zona fasciculata-reticularis cells (45) and adrenocortical adenoma cells with Cushing's syndrome in response to ACTH (14), as well as in human monocytes (6) and rat thymocytes (1). In the present study, the shift of PKC localization was not observed in the adrenocortical adenomas, whereas the immunoreactivity in pheochromocytoma and neuroblastoma was present in the particulate membrane fraction.…”

Section: Discussionmentioning

confidence: 48%

Immunohistochemical evidence for protein kinase C in primary human adrenal tumors.

Shigematsu

Katamine

Nakatani

et al. 1992

Acta Histochem. Cytochem

View full text Add to dashboard Cite

We investigated the specific expression of protein kinase C (PKC) in primary human adrenal tumors resected surgically, using type-specific monoclonal antibodies MC-1a, -2a and -3a. Included were adrenocortical adenomas (Cushing's syndrome, Conn's syndrome and clinical nonfunctioning), pheochromocytoma and neuroblastoma.Immunoblotting experiments revealed that the adrenal cortex, medulla, adrenocortical adenomas and pheochromocytoma contained type III isozyme as the major subtype, whereas the neuroblastoma expressed both types II and III isozymes. PKC specific antibodies recognized two bands with a molecular mass of 79 and 81 kDa. Immunoreactivity was mainly present in the cytosolic fraction of the adrenal cortex, medulla and adrenocortical adenomas. The translocation of PKC from cytosol to particulate membrane fractions was observed in cases of pheochromocytoma and neuroblastoma.Microscopically, strong immunostaining was present in the zona fasciculata to reticularis of the adrenal cortex, while the zona glomerulosa and medulla demonstrated minimal staining. The intermediate-type and compact-type cells of adrenocortical adenomas gave a strong positive reaction. The MC-2a positive cells of neuroblastoma were limited to the perivascular area. Immunoblotting and electron microscopic observations of the adrenocortical and adenoma cells showed immunoreactive products on the endoplasmic reticulum, mitochondria and plasma membrane, with a different intensity. In addition to the hypothesis that PKC may play an important role in the regulation of steroidogenesis and catecholamine secretion, our results indicate that the localization of PKC differs in tumors derived from adrenocortical and medullary cells. The possibility that the expression of type II isozyme in neuroblastoma may be associated with neural differentiation would have to be considered.Protein kinase C (PKC) originally identified as an ubiquitous serine and threonine-specific protein kinase seems to play an important role in the signal transduction pathway leading to differentiation, hormone and neurotransmitter release, sensory transduction, and gene expression (29, 30,43). Although PKC is mostly confined to the central nervous system, a variety of peripheral tissues including the adrenal gland also possesses PKC activity (18, 20, 31, 33, 35,45). Adrenocortical function is regulated especially by ACTH and angiotensin II (All) (42). In eliciting the steroidogenic response, ACTH induces a protein phosphorylation as well as a cAMP production (11), whereas All stimulates the efflux of calcium from intracellular and extracellular pool following to rise in inositol trisphosphate (9, 10). The phorbol ester, 12-0-tetradecanoyl phorbol-l3-acetate (TPA), an activator of PKC (3), and All analog, together, induces aldosterone secretion from adrenal glomerulosa cells (19). Long-term treatment with TPA has been suggested to inhibit cortisol and androgen biosynthesis (26, 28). On the other hand, the regulation of catecholamine secretion and neural differentiation by PKC h...

show abstract

Section: Discussionmentioning

confidence: 48%