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The Nuclear Receptor NR2F2 Activates Star Expression and Steroidogenesis in Mouse MA-10 and MLTC-1 Leydig Cells1

Mendoza-Villarroel, Raifish E., Robert, Nicholas M., Martin, Luc J., Brousseau, Catherine, Tremblay, Jacques J.·2014·Biology of Reproduction
DOI 10.1095/biolreprod.113.115790
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Abstract

Testosterone production is dependent on cholesterol transport within the mitochondrial matrix, an essential step mediated by a protein complex containing the steroidogenic acute regulatory (STAR) protein. In steroidogenic Leydig cells, Star expression is hormonally regulated and involves several transcription factors. NR2F2 (COUP-TFII) is an orphan nuclear receptor that plays critical roles in cell differentiation and lineage determination. Conditional NR2F2 knockout prior to puberty leads to male infertility due to insufficient testosterone production, suggesting that NR2F2 could positively regulate steroidogenesis and Star expression. In this study we found that NR2F2 is expressed in the nucleus of some peritubular myoid cells and in interstitial cells, mainly in steroidogenically active adult Leydig cells. In MA-10 and MLTC-1 Leydig cells, small interfering RNA (siRNA)-mediated NR2F2 knockdown reduces basal steroid production without affecting hormone responsiveness. Consistent with this, we found that STAR mRNA and protein levels were reduced in NR2F2-depleted MA-10 and MLTC-1 cells. Transient transfections of Leydig cells revealed that a -986 bp mouse Star promoter construct was activated 3-fold by NR2F2. Using 5' progressive deletion constructs, we mapped the NR2F2-responsive element between -131 and -95 bp. This proximal promoter region contains a previously uncharacterized direct repeat 1 (DR1)-like element to which NR2F2 is recruited and directly binds. Mutations in…

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Metadata

Authors
Mendoza-Villarroel, R. E., Robert, N. M., Martin, L. J., Brousseau, C., & Tremblay, J. J.
Venue
Biology of Reproduction
Publisher
Oxford University Press (OUP)
Published
2014-07-01
Volume
91
Issue
1
ISSN
  • 0006-3363
  • 1529-7268
DOI
10.1095/biolreprod.113.115790
Cited by
48
References
7
Language
en

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