Activin A (a homodimer of two activin betaA subunits) has been shown to induce the neuronal differentiation of rat pheochromocytoma PC12 cells. We studied activin A and its receptor gene expression in human pheochromocytomas in vivo and in vitro to clarify the potential involvement of activin A in the pathophysiology of these tumors. We first screened 20 pheochromocytomas and nine normal adrenal tissues for activin betaA mRNA expression. Northern blots hybridized with specific oligonucleotide probes detected weak signals for activin betaA transcripts in pheochromocytomas. Both type I and type II activin receptor (ActR-I, ActR-IB and ActR-II) mRNA expression was also detectable in the pheochromocytoma tissues. In primary cultures of pheochromocytoma cells, expression of activin betaA mRNA was readily detectable by Northern blotting, and secretion of activin A into the conditioned medium was confirmed by an enzyme-linked immunosorbent assay. The expression of activin betaA mRNA and secretion of activin A were induced by (Bu)(2)cAMP after 1 and 3 days of treatment (all P<0.05). A protein kinase inhibitor, staurosporine, inhibited the basal and (Bu)(2)cAMP-induced accumulation of activin betaA mRNA (P<0.05). In addition, induction of chromaffin phenotype by dexamethasone also inhibited the basal and (Bu)(2)cAMP-induced expression of activin A at both mRNA and protein levels (all P<0.05). In contrast, the expression of ActR-I and ActR-IB mRNAs was not affected by these agents in cultured pheochromocytoma cells. In summary, activin betaA subunit and activin receptors are expressed in human pheochromocytomas. Production of activin A in cultured pheochromocytoma cells is induced through the protein kinase A pathway, but reduced during chromaffin differentiation. Therefore, activin A may function as a local neurotrophic factor via an auto/paracrine manner in human pheochromocytomas.

This article has been cited by other articles:

				D. J Keating and C. Chen Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism J. Endocrinol., August 1, 2005; 186(2): R1 - R5. [Abstract] [Full Text] [PDF]

				D. C. Danila, X. Zhang, Y. Zhou, J. N. S. Haidar, and A. Klibanski Overexpression of Wild-Type Activin Receptor Alk4-1 Restores Activin Antiproliferative Effects in Human Pituitary Tumor Cells J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4741 - 4746. [Abstract] [Full Text] [PDF]

				R. G. Rodrigues, A. Panizo-Santos, J. A. Cashel, H. C. Krutzsch, M. J. Merino, and D. D. Roberts Semenogelins Are Ectopically Expressed in Small Cell Lung Carcinoma Clin. Cancer Res., April 1, 2001; 7(4): 854 - 860. [Abstract] [Full Text]