Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase

N. Hiroi, T. Kino, M. Bassett, W. E. Rainey, M. Phung, M. Abu-Asab, T. Fojo, P. Briata, G. P. Chrousos, S. R. Bornstein

Research output: Contribution to journalArticle

Abstract

Pituitary homeobox 1 (Ptx1/Pitx1) is a homeodomain-containing transcription factor present throughout pituitary development. Ptx1/Pitx1 interacts with steroidogenic factor 1 (SF-1) in the regulation of pituitary gene expression. SF-1 also plays a critical role in the transcription of enzymes involved in adrenal steroidogenesis. Therefore, we analyzed the presence and role of Ptx1/Pitx1 in human adrenal cortex. Both Ptx1/Pitx1 and SF-1 mRNA were expressed in the human adrenal gland, and immuno-electron microscopy demonstrated the presence of Ptx1/Pitx1 protein in the nucleus of adrenocortical cells. Computer analysis revealed the presence of Ptx1/Pitx1 signal sequences within the promoter region of human 11β hydroxylase (hCYP11B1). To examine the role of Ptx1/Pitx1 in the regulation of the genes, we prepared reporter constructs using the 5′-flanking DNA of the hCYP11B1 gene and transfected them into Y-1 mouse adrenocortical cells, HeLa and CV-1 cells. Ptx1/Pitx1 stimulation of hCYP11B1 reporter activity (3-fold over basal) in Y-1 cells was equal to that observed with SF-1. The hCYP11B1 promoter activity in Y-1 cells was not synergistically increased by co-transfection with both Ptx1/Pitx1 and SF-1. Both basal and ACTH-stimulated hCYP11B1 reporter activities in Y-1 cells were increased by co-transfection with either Ptx1/ Pitx1 or SF-1 expression vectors. In contrast, co-transfection with both Ptx1/Pitx1 and SF-1 synergistically increased hCYP11B1 promoter activity in HeLa and CV-1 cells (5-fold and 20-fold over basal, respectively). In conclusion, this study represents the first demonstration for a role of Ptx1/Pitx1 in the regulation of transcription of enzymes involved in adrenal steroidogenesis.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalHormone and Metabolic Research
Volume35
Issue number5
DOIs
Publication statusPublished - May 1 2003

    Fingerprint

Keywords

  • 11β-hydroxylase
  • Pituitary Homeobox Factor 1 Ptx1/Pitx1
  • Steroidogenic Factor 1 (SF-1)

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Hiroi, N., Kino, T., Bassett, M., Rainey, W. E., Phung, M., Abu-Asab, M., Fojo, T., Briata, P., Chrousos, G. P., & Bornstein, S. R. (2003). Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase. Hormone and Metabolic Research, 35(5), 273-278. https://doi.org/10.1055/s-2003-41301