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The Urokinase-Type Plasminogen Activator Contributes to cAMP-Induced Steroidogenesis in MA-10 Leydig Cells
- Source :
- Endocrines, Vol 3, Iss 3, Pp 460-475 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Leydig cells produce androgens which are essential for male sex differentiation and reproductive functions. Steroidogenesis, as well as expression of several genes in Leydig cells, are stimulated by LH/cAMP and repressed by AMP/AMPK. One of those genes is Plau, which codes for the urokinase-type plasminogen activator (uPA), a secreted serine protease. The role of uPA and the regulation of Plau expression in Leydig cells remain unknown. Using siRNA-mediated knockdown, uPA was required for maximal cAMP-induced STAR and steroid hormone production in MA-10 Leydig cells. Analysis of Plau mRNA levels and promoter activity revealed that its expression is strongly induced by cAMP; this induction is blunted by AMPK. The cAMP-responsive region was located, in part, in the proximal Plau promoter that contains a species-conserved GC box at −56 bp. The transcription factor Krüppel-like factor 6 (KLF6) activated the Plau promoter. Mutation of the GC box at −56 bp abolished KLF6-mediated activation and significantly reduced cAMP-induced Plau promoter activity. These data define a role for uPA in Leydig cell steroidogenesis and provide insights into the regulation of Plau gene expression in these cells.
Details
- Language :
- English
- ISSN :
- 2673396X
- Volume :
- 3
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Endocrines
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.13056404c4264497be7c3f065dce90a5
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/endocrines3030037