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POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells
M M França1, N P Abreu1, T A M Vrechi1
1Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
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.
Insights
The transcription factor POD-1 (also known as TCF21) regulates SF-1 expression differently in normal rat adrenal cortex zones. POD-1 overexpression reduced SF-1 in fasciculata/reticularis cells but not glomerulosa cells.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- The transcription factor POD-1 (TCF21) is known to negatively regulate SF-1 (NR5A1) expression, impacting adrenal development and tumorigenesis.
- SF-1 is crucial for adrenal cell proliferation, and its dysregulation is linked to adrenal tumors.
- The precise role of POD-1 in modulating SF-1 in normal adrenal cells remains unclear.
Purpose of the Study:
- To investigate the basal expression of POD-1 and SF-1 in distinct zones of the normal rat adrenal cortex.
- To determine if POD-1 overexpression affects endogenous SF-1 levels and its target gene expression in primary adrenal cells.
- To elucidate zone-specific responses to POD-1 modulation in the adrenal cortex.
Main Methods:
- Primary cultures of rat glomerulosa (G) and fasciculata/reticularis (F/R) adrenal cells were established.
- Overexpression of POD-1 was achieved via transfection with pCMVMycPod-1.
- Quantitative analysis of SF-1, StAR, and CYP11B2 mRNA and protein levels was performed.
Main Results:
- POD-1 overexpression significantly decreased SF-1 mRNA and protein levels in F/R cells, but not in G cells.
- The expression of the SF-1 target gene StAR was reduced in F/R cells following POD-1 overexpression.
- No modulation of SF-1 targets (StAR, CYP11B2) was observed in G cells upon POD-1 overexpression.
Conclusions:
- Glomerulosa and fasciculata/reticularis cells exhibit differential responses to ectopic POD-1 expression, highlighting functional zonation within the adrenal cortex.
- These findings support the hypothesis that POD-1/TCF21 regulates SF-1 in normal adrenocortical cells.
- The study provides insights into the distinct regulatory mechanisms governing SF-1 in different adrenal zones.
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