Endocrinology, Vol 130, 2745-2750, Copyright © 1992 by Endocrine Society

ARTICLES

Cyclic adenosine 3',5'-monophosphate negatively regulates clusterin gene expression in Leydig tumor cell lines

OP Pignataro, ZM Feng and CL Chen
Population Council, New York, New York 10021.

The clusterin protein and its messenger RNA were identified in many tissues including testis. In this report, we demonstrate the expression of clusterin gene in four Leydig tumor cell lines, including mouse MA- 10 and I-10 and rat R2C and LC-540. When the cells were incubated with 0.1 mM 8-bromo-cAMP or (Bu)2cAMP for 17 h, an unexpected, profound suppression of clusterin mRNA accumulation was observed. A 60-70% decrease in clusterin mRNA was observed in MA-10 and R2C cells, 10% in I-10 cells, and no apparent change in LC-540 cells. The inhibitory effect of cAMP was specific to the clusterin gene, since in the same cells cholesterol side-chain cleavage enzyme mRNA was drastically elevated in MA-10 and I-10 cells while alpha-tubulin mRNA levels were not changed in all four cell lines. The reduction could be detected as early as 4 h, and was evident at 17 h after cAMP administration. Removal of cAMP from culture media at 17 h prevented the decline of clusterin mRNA. The suppression of clusterin gene expression can also be demonstrated by treatment with human CG or forskolin, which were known to elevate intracellular cAMP levels. Our observations suggest: 1) cAMP negatively regulates clusterin gene expression in two Leydig tumor cell lines, MA-10 and R2C; 2) The inhibitory effect of cAMP on clusterin gene expression is probably acting through the protein kinase A pathway; and 3) The four Leydig tumor cell lines respond differently to cAMP in the expression of clusterin and side-chain cleavage genes.

This article has been cited by other articles:

				Z. Zhang, A. Z. Wu, Z.-M. Feng, D. Mruk, C. Y. Cheng, and C.-L. C. Chen Gonadotropins, via cAMP, Negatively Regulate GATA-1 Gene Expression in Testicular Cells Endocrinology, March 1, 2002; 143(3): 829 - 836. [Abstract] [Full Text] [PDF]

				M. Magnanti, O. Gandini, L. Giuliani, P. Gazzaniga, H. H. Marti, A. Gradilone, L. Frati, A. M. Agliano, and M. Gassmann Erythropoietin expression in primary rat Sertoli and peritubular myoid cells Blood, November 1, 2001; 98(9): 2872 - 2874. [Abstract] [Full Text] [PDF]

				Z.-M. Feng, A. Z. Wu, Z. Zhang, and C.-L. C. Chen GATA-1 and GATA-4 Transactivate Inhibin/Activin {beta}-B-Subunit Gene Transcription in Testicular Cells Mol. Endocrinol., November 1, 2000; 14(11): 1820 - 1835. [Abstract] [Full Text]

				C Jomary, G Chatelain, D Michel, A Weston, M. Neal, and S. Jones Effect of targeted expression of clusterin in photoreceptor cells on retinal development and differentiation J. Cell Sci., January 5, 1999; 112(10): 1455 - 1464. [Abstract] [PDF]

				Z.-M. Feng, A. Z. Wu, and C.-L. C. Chen Testicular GATA-1 Factor Up-Regulates the Promoter Activity of Rat Inhibin {alpha}-Subunit Gene in MA-10 Leydig Tumor Cells Mol. Endocrinol., March 1, 1998; 12(3): 378 - 390. [Abstract] [Full Text]

				M Brignoni, O. Pignataro, M. Rodriguez, A Alvarez, D. Vega-Salas, E Rodriguez-Boulan, and P. Salas Cyclic AMP modulates the rate of 'constitutive' exocytosis of apical membrane proteins in Madin-Darby canine kidney cells J. Cell Sci., January 5, 1995; 108(5): 1931 - 1943. [Abstract] [PDF]