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Blocking L-type calcium channels reduced the threshold of cAMP-induced steroidogenic acute regulatory gene expression

Akhilesh K Pandey1, Wei Li, Xiangling Yin

  • 1Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.

The Journal of Endocrinology
|October 14, 2009
PubMed

Insights

Blocking calcium (Ca2+) influx via L-type channels enhances steroidogenic acute regulatory (STAR) protein expression in Leydig cells. This reveals a novel inhibitory role for Ca2+ in STAR gene regulation and steroidogenesis.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Physiology

Background:

  • Calcium ions (Ca2+) play established roles in steroidogenesis.
  • The precise mechanisms by which Ca2+ influences steroidogenic gene expression remain incompletely understood.

Purpose of the Study:

  • To investigate the inhibitory effect of Ca2+ influx through L-type Ca2+ channels on the gene expression of steroidogenic acute regulatory (STAR) protein.
  • To elucidate the molecular mechanisms underlying Ca2+ regulation of STAR gene transcription in MA-10 mouse Leydig cells.

Main Methods:

  • Utilized selective L-type Ca2+ channel blockers (e.g., nifedipine) in MA-10 mouse Leydig cells.
  • Assessed STAR protein expression, progesterone production, Star mRNA levels via RT-PCR, and Star promoter activity using luciferase assays.
  • Investigated the role of DAX-1 (NR0B1) protein expression.

Main Results:

  • Blocking Ca2+ influx through L-type channels significantly enhanced cAMP-induced STAR protein expression and progesterone production.
  • Ca2+ channel blockade acted at the level of Star gene transcription, reducing DAX-1 repressor activity.
  • A synergistic interaction between nifedipine and cAMP was observed, lowering the cAMP threshold for steroidogenesis.

Conclusions:

  • Ca2+ influx via L-type Ca2+ channels exerts an inhibitory effect on Star gene expression.
  • Blocking these channels attenuates inhibition and reduces the cAMP induction threshold for Star gene expression in Leydig cells.
  • This highlights a novel regulatory pathway for steroidogenesis involving L-type calcium channels.

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