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  Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis.

Lichtenauer, U. D., Duchniewicz, M., Kolanczyk, M., Hoeflich, A., Hahner, S., Else, T., et al. (2007). Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. Endocrinology: Official Journal of the Endocrine Society, 148(2), 693-704. doi:10.1210/en.2006-0681.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8254-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8255-C
Genre: Journal Article
Alternative Title : Endocrinology

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 Creators:
Lichtenauer, Urs D., Author
Duchniewicz, Marlena, Author
Kolanczyk, Mateusz1, Author              
Hoeflich, Andreas, Author
Hahner, Stephanie, Author
Else, Tobias, Author
Bicknell, Andrew B., Author
Zemojtel, Tomasz2, Author              
Stallings, Nancy R., Author
Schulte, Dominik M., Author
Kamps, Mark P., Author
Hammer, Gary D., Author
Scheele, Jürgen S., Author
Beuschlein, Felix, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              

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 Abstract: A variety of transcription factors including Wilms tumor gene (Wt-1), steroidogenic factor 1 (Sf-1), dosage-sensitive sex reversal, adrenal hypoplasia congenita on the X-chromosome, Gene 1 (Dax-1), and pre-B-cell transcription factor 1 (Pbx1) have been defined as necessary for regular adrenocortical development. However, the role of Pbx1 for adrenal growth and function in the adult organism together with the molecular relationship between Pbx1 and these other transcription factors have not been characterized. We demonstrate that Pbx haploinsufficiency (Pbx1+/–) in mice is accompanied by a significant lower adrenal weight in adult animals compared with wild-type controls. Accordingly, baseline proliferating cell nuclear antigen levels are lower in Pbx1+/– mice, and unilateral adrenalectomy results in impaired contralateral compensatory adrenal growth, indicating a lower proliferative potential in the context of Pbx1 haploinsufficiency. In accordance with the key role of IGFs in adrenocortical proliferation and development, real-time RT-PCR demonstrates significant lower expression levels of the IGF-I receptor, and up-regulation of IGF binding protein-2. Functionally, Pbx1+/– mice display a blunted corticosterone response after ACTH stimulation coincident with lower adrenal expression of the ACTH receptor (melanocortin 2 receptor, Mc2-r). Mechanistically, in vitro studies reveal that Pbx1 and Sf-1 synergistically stimulates Mc2-r promoter activity. Moreover, Sf-1 directly activates the Pbx1 promoter activity in vitro and in vivo. Taken together, these studies provide evidence for a role of Pbx1 in the maintenance of a functional adrenal cortex mediated by synergistic actions of Pbx1 and Sf-1 in the transcriptional regulation of the critical effector of adrenocortical differentiation, the ACTH receptor.

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Language(s): eng - English
 Dates: 2007-02-01
 Publication Status: Published in print
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Title: Endocrinology : Official Journal of the Endocrine Society
  Alternative Title : Endocrinology
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 148 (2) Sequence Number: - Start / End Page: 693 - 704 Identifier: ISSN: 0013-7227