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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0206v1 204/1/67    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pandey, A. Articles by Wang, X. PubMed PubMed Citation Articles by Pandey, A. Articles by Wang, X.

A Pandey, Texas Tech University Health Sciences Center, Lubbock, United States
W Li, Texas Tech University Health Sciences Center, Lubbock, United States
X Yin, Texas Tech University Health Sciences Center, Lubbock, United States
D Stocco, Texas Tech University Health Sciences Center, Lubbock, United States
P Grammas, Texas Tech University Health Sciences Center, Lubbock, United States
X Wang, Lubbock, United States

XingJia Wang, Email: xingjia.wang{at}ttuhsc.edu

Previous studies have reported the roles of Ca2+ in steroidogenesis. The present study has investigated an inhibitory effect of Ca2+ influx through L-type Ca2+ channels on gene expression of steroidogenic acute regulatory (StAR) protein that regulates the transfer of substrate cholesterol to the inner mitochondrial membrane for steroidogenesis. Blocking Ca2+ influx through L-type Ca2+ channels using the selective Ca2+ channel blocker, nifedipine, markedly enhanced cAMP-induced StAR protein expression and progesterone production in MA-10 mouse Leydig cells. This was confirmed by utilization of different L-type Ca2+ channel blockers. RT-PCR analyses of Star mRNA and luciferase assays of Star promoter activity indicated that blocking Ca2+ influx through L-type Ca2+ channel acted at the level of Star gene transcription. Further studies showed that blocking the Ca2+ channel enhanced Star gene transcription by depressing expression of DAX-1 protein, a transcriptional repressor of Star gene expression. It was also observed that there is a synergistic interaction between nifedipine and cAMP. Normally, sub-threshold levels of cAMP are unable to induce steroidogenesis, but in the presence of the L-type Ca2+ channel blocker, they increased StAR protein and steroid hormone to the maximal levels. However, in the absence of minimal levels of cAMP, none of the L-type Ca2+ channel blockers is able to induce Star gene expression. These observations indicate that Ca2+ influx through L-type Ca2+ channels is involved in an inhibitory effect on Star gene expression. Blocking L-type Ca2+ channel attenuated the inhibition and reduced the threshold of cAMP-induced Star gene expression in Leydig cells.