This Article Full Text Full Text (PDF) All Versions of this Article: 145/2/508    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Val, P. Articles by Martinez, A. Search for Related Content PubMed PubMed Citation Articles by Val, P. Articles by Martinez, A.

Adrenocorticotropin/3',5'-Cyclic AMP-Mediated Transcription of the Scavenger akr1-b7 Gene in Adrenocortical Cells Is Dependent on Three Functionally Distinct Steroidogenic Factor-1-Responsive Elements

Unité Mixte de Recherche Centre National de la Recherche Scientifique, Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, 63177 Aubière, France

Address all correspondence and requests for reprints to: Prof. Anne-marie Lefrançois-Martinez, Unité Mixte de Recherche Centre National de la Recherche Scientifique, 6547 Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Clermont II, Complexe Universitaire des Cézeaux, 24 avenue des Landais, 63177 Aubière cedex, France. E-mail: a-marie.lefrancois-martinez{at}geem.univ-bpclermont.fr.

The akr1-b7 gene encodes a scavenger enzyme expressed in steroidogenic glands under pituitary control. In the zona fasciculata of the adrenal cortex where its expression is controlled by ACTH, AKR1-B7 detoxifies isocaproaldehyde produced during the first step of steroidogenesis. Three steroidogenic factor-1 (SF-1)-responsive elements (SFREs) are contained within the -510/+41 promoter region, which was previously demonstrated to drive gene expression in transgenic mice adrenal cortex. All these sequences bind at least SF-1 in Y1 adrenocortical cell nuclear extracts and can be activated by overexpression of this factor in HeLa cells. However, the three SFREs show distinct properties regarding akr1-b7 promoter activity in Y1 cells. Whereas the proximal -102 SFRE supports basal promoter activity, the -458 bona fide SFRE is essential for both basal promoter activity and cAMP responsiveness, although it is unresponsive to cAMP when isolated from its promoter context. This suggests that SF-1 is not a cAMP-responsive factor per se. The neighboring SFRE at -503 is a palindromic sequence that binds monomeric and heteromeric SF-1 as well as an adrenal-specific complex. Using MA-10 Leydig cells and Y1–10r9 mutant cells, we provide evidence that its activity in adrenocortical cells depends on the binding of the adrenal-specific factor, which is required for basal and cAMP-induced promoter activity. Furthermore, the -503 site has intrinsic cAMP-sensing ability in Y1 cells, which is correlated with increased adrenal-specific complex binding. Collectively, our results suggest that cAMP responsiveness of the akr1-b7 promoter is achieved through cooperation between the adrenal-specific factor bound to the -503 site and SF-1 bound to the -458 site.

This article has been cited by other articles:

				C Baumann, B Davies, M Peters, U Kaufmann-Reiche, M Lessl, and F Theuring AKR1B7 (mouse vas deferens protein) is dispensable for mouse development and reproductive success Reproduction, July 1, 2007; 134(1): 97 - 109. [Abstract] [Full Text] [PDF]

				J. Tirard, J. Gout, A. M. Lefrancois-Martinez, A. Martinez, M. Begeot, and D. Naville A Novel Inhibitory Protein in Adipose Tissue, the Aldo-Keto Reductase AKR1B7: Its Role in Adipogenesis Endocrinology, May 1, 2007; 148(5): 1996 - 2005. [Abstract] [Full Text] [PDF]

				B. Ragazzon, A.-M. Lefrancois-Martinez, P. Val, I. Sahut-Barnola, C. Tournaire, C. Chambon, J.-L. Gachancard-Bouya, R.-J. Begue, G. Veyssiere, and A. Martinez Adrenocorticotropin-Dependent Changes in SF-1/DAX-1 Ratio Influence Steroidogenic Genes Expression in a Novel Model of Glucocorticoid-Producing Adrenocortical Cell Lines Derived from Targeted Tumorigenesis Endocrinology, April 1, 2006; 147(4): 1805 - 1818. [Abstract] [Full Text] [PDF]