小川 貴美雄

Protein kinase A (PICA) regulatory subunit type I alpha (RI alpha) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RI alpha expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RI alpha expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RI alpha expression. PKA activities were determined in several adenomas highly expressing RI alpha. RI alpha expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RI alpha, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RI alpha in 20 out of 22 adenomas. In adenomas, the greater RI alpha expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RI alpha expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.