TY - JOUR
T1 - Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11β-hydroxylase
AU - Hiroi, N.
AU - Kino, T.
AU - Bassett, M.
AU - Rainey, W. E.
AU - Phung, M.
AU - Abu-Asab, M.
AU - Fojo, T.
AU - Briata, P.
AU - Chrousos, G. P.
AU - Bornstein, S. R.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
KW - 11β-hydroxylase
KW - Pituitary Homeobox Factor 1 Ptx1/Pitx1
KW - Steroidogenic Factor 1 (SF-1)
UR - http://www.scopus.com/inward/record.url?scp=10744228960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744228960&partnerID=8YFLogxK
U2 - 10.1055/s-2003-41301
DO - 10.1055/s-2003-41301
M3 - Article
C2 - 12915995
AN - SCOPUS:10744228960
VL - 35
SP - 273
EP - 278
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
SN - 0018-5043
IS - 5
ER -