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

N. Hiroi, Tomoshige 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

6 Citations (Scopus)

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 - 1 May 2003
Externally publishedYes

Fingerprint

Steroid 11-beta-Hydroxylase
Steroidogenic Factor 1
Homeobox Genes
Transcription Factors
Transfection
Transcription
Genes
Immunoelectron Microscopy
Adrenal Cortex
Gene Expression Regulation
Enzymes
Adrenal Glands
Protein Sorting Signals
Mixed Function Oxygenases
Cell Nucleus
Reporter Genes
HeLa Cells
Genetic Promoter Regions
Gene expression
Adrenocorticotropic Hormone

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase. / Hiroi, N.; Kino, Tomoshige; Bassett, M.; Rainey, W. E.; Phung, M.; Abu-Asab, M.; Fojo, T.; Briata, P.; Chrousos, G. P.; Bornstein, S. R.

In: Hormone and Metabolic Research, Vol. 35, No. 5, 01.05.2003, p. 273-278.

Research output: Contribution to journalArticle

Hiroi, N, Kino, T, Bassett, M, Rainey, WE, Phung, M, Abu-Asab, M, Fojo, T, Briata, P, Chrousos, GP & Bornstein, SR 2003, 'Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase', Hormone and Metabolic Research, vol. 35, no. 5, pp. 273-278. https://doi.org/10.1055/s-2003-41301
Hiroi, N. ; Kino, Tomoshige ; Bassett, M. ; Rainey, W. E. ; Phung, M. ; Abu-Asab, M. ; Fojo, T. ; Briata, P. ; Chrousos, G. P. ; Bornstein, S. R. / Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase. In: Hormone and Metabolic Research. 2003 ; Vol. 35, No. 5. pp. 273-278.
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