title: POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells.
abstract: During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G) and fasciculata/reticularis (F/R) cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: M M
authors.initials: MM
authors.lastname: França
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: N P
authors.initials: NP
authors.lastname: Abreu
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: T A M
authors.initials: TA
authors.lastname: Vrechi
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: C F
authors.initials: CF
authors.lastname: Lotfi
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D015151:Immunoblotting; D008297:Male; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000032:analysis; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054339:Steroidogenic Factor 1 / Q000032:analysis / Q000378:metabolism*; D015383:Zona Fasciculata / Q000166:cytology / Q000378:metabolism; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism; D015385:Zona Reticularis / Q000166:cytology / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D054339:Steroidogenic Factor 1; D000098682:Steroidogenic Acute Regulatory Protein; C491824:Tcf21 protein, rat