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

Urs D. Lichtenauer, Marlena Duchniewicz, Mateusz Kolanczyk, Andreas Hoeflich, Stephanie Hahner, Tobias Else, Andrew B. Bicknell, Tomasz Zemojtel, Nancy R. Stallings, Dominik M. Schulte, Mark P. Kamps, Gary D. Hammer, Jürgen S. Scheele, Felix Beuschlein

Research output: Contribution to journalArticle

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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.Wedemonstrate 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.

Original languageEnglish (US)
Pages (from-to)693-704
Number of pages12
JournalEndocrinology
Volume148
Issue number2
DOIs
StatePublished - Feb 2007

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Steroidogenic Factor 1
B-Lymphoid Precursor Cells
Receptor, Melanocortin, Type 2
Transcription Factors
Corticotropin Receptors
Haploinsufficiency
Growth
Wilms' Tumor Genes
Insulin-Like Growth Factor Binding Protein 2
X-Linked Genes
IGF Type 1 Receptor
Chromosomes, Human, Pair 1
Adrenal Cortex
Adrenalectomy
Proliferating Cell Nuclear Antigen
Corticosterone
Adrenocorticotropic Hormone
Real-Time Polymerase Chain Reaction
Up-Regulation
Maintenance

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Lichtenauer, U. D., Duchniewicz, M., Kolanczyk, M., Hoeflich, A., Hahner, S., Else, T., ... Beuschlein, F. (2007). Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. Endocrinology, 148(2), 693-704. https://doi.org/10.1210/en.2006-0681

Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. / Lichtenauer, Urs D.; Duchniewicz, Marlena; Kolanczyk, Mateusz; Hoeflich, Andreas; Hahner, Stephanie; Else, Tobias; Bicknell, Andrew B.; Zemojtel, Tomasz; Stallings, Nancy R.; Schulte, Dominik M.; Kamps, Mark P.; Hammer, Gary D.; Scheele, Jürgen S.; Beuschlein, Felix.

In: Endocrinology, Vol. 148, No. 2, 02.2007, p. 693-704.

Research output: Contribution to journalArticle

Lichtenauer, UD, Duchniewicz, M, Kolanczyk, M, Hoeflich, A, Hahner, S, Else, T, Bicknell, AB, Zemojtel, T, Stallings, NR, Schulte, DM, Kamps, MP, Hammer, GD, Scheele, JS & Beuschlein, F 2007, 'Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis', Endocrinology, vol. 148, no. 2, pp. 693-704. https://doi.org/10.1210/en.2006-0681
Lichtenauer, Urs D. ; Duchniewicz, Marlena ; Kolanczyk, Mateusz ; Hoeflich, Andreas ; Hahner, Stephanie ; Else, Tobias ; Bicknell, Andrew B. ; Zemojtel, Tomasz ; Stallings, Nancy R. ; Schulte, Dominik M. ; Kamps, Mark P. ; Hammer, Gary D. ; Scheele, Jürgen S. ; Beuschlein, Felix. / Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. In: Endocrinology. 2007 ; Vol. 148, No. 2. pp. 693-704.
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