title: SF-1 (NR5A1) expression is stimulated by the PKA pathway and is essential for the PKA-induced activation of LIPE expression in Y-1 cells.
abstract: In the adrenal cortex, corticotropin induces the expression of several genes encoding proteins involved in the synthesis and intracellular transport of steroid hormones via the protein kinase A (PKA) signalling pathway, and this process is mediated by steroidogenic factor-1 (SF-1). This study was designed to elucidate the influence of the PKA and PKC pathways on the expression of the SF-1 gene in mouse adrenocortical cells, line Y-1. It has also been attempted to answer the question whether or not SF-1 plays a role in the PKA-induced expression of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase, which supplies cholesterol for steroid hormone synthesis. In this study, we found that stimulation of the PKA pathway caused a significant increase in SF-1 expression, and that this effect was abolished by the PKA inhibitor, H89. Decreased SF-1 gene transcript levels were seen with the simultaneous activation of PKA and PKC, suggesting a possible interaction between the PKA and PKC pathways. It was also observed that SF-1 increased the transcriptional activity of the LIPE gene by interacting with the SF-1 response element located in promoter A. Moreover, transient silencing of SF-1 expression with specific siRNAs abolished PKA-stimulated transcription of the LIPE gene, indicating that SF-1 is an important regulator of LIPE expression in Y-1 cells and thus could play a role in the regulation of the cholesterol supply for adrenal steroidogenesis.
authors.affiliation: Department of Cancer Immunology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kulcenty
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781, Poznan, Poland. mholysz@ump.edu.pl.
authors.forename: M
authors.identifier: http://orcid.org/0000-0003-2505-3582
authors.initials: M
authors.lastname: Holysz
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781, Poznan, Poland.
authors.forename: W H
authors.initials: WH
authors.lastname: Trzeciak
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D054339:Steroidogenic Factor 1 / Q000235:genetics* / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D054339:Steroidogenic Factor 1; D013449:Sulfonamides; C515058:steroidogenic factor 1, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002787:Sterol Esterase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: HSL; LIPE; PKA; SF-1; Y-1 cells