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.
Highlights
The synthesis and secretion of steroid hormones in the adrenal cortex is regulated by corticotropin (ACTH), secreted by the anterior pituitary
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 (SF1)
These actions are mediated by steroidogenic factor-1 (SF-1), which induces the expression of genes encoding members of the cytochrome P450 (CYP) superfamily, as well as the genes encoding ACTH receptor, and transporting proteins including steroidogenic acute regulator (StAR) [4,5,6]
Summary
The synthesis and secretion of steroid hormones in the adrenal cortex is regulated by corticotropin (ACTH), secreted by the anterior pituitary. ACTH acts via the PKA pathway to induce the expression of genes encoding proteins involved in the synthesis and intracellular transport of steroid hormones [1,2,3] as well as the supply of substrate, cholesterol, stored in lipid droplets. These actions are mediated by steroidogenic factor-1 (SF-1), which induces the expression of genes encoding members of the cytochrome P450 (CYP) superfamily, as well as the genes encoding ACTH receptor, and transporting proteins including steroidogenic acute regulator (StAR) [4,5,6]. Numerous investigations have shown that HSL is activated by the covalent phosphorylation of Ser563 and Ser660 residues in its regulatory domain These reactions are catalysed by a cAMP-
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