ArticleThe Journal of biological chemistry2013
Mechanisms of action of hormone-sensitive lipase in mouse Leydig cells: its role in the regulation of the steroidogenic acute regulatory protein.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
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- Nano Spirulina platensis countered cisplatin-induced repro-toxicity by reversing the expression of altered steroid hormones and downregulation of the StAR gene.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The consequences of climate change and male reproductive health: A review of the possible impact and mechanisms.Biochemistry and biophysics reports · 2025Review
- Transcriptomic analysis reveals suppression of steroidogenic acute regulatory protein in gender-specific differences in Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Reducing the lipase LIPE in mutant α-synuclein mice improves Parkinson-like deficits and reveals sex differences in fatty acid metabolism.Neurobiology of disease · 2024Article
- Acetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17β-Estradiol Regulation in Hormone-Sensitive Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Differential regulation of STARD1, STARD4 and STARD6 in the human ovary.The Journal of endocrinology · 2024Article
- Developmental and adult stress: effects of steroids and neurosteroids.Stress (Amsterdam, Netherlands) · 2024Review
- Epigenetic Dysregulation and Its Correlation with the Steroidogenic Machinery Impacting Breast Pathogenesis: Data Mining and Molecular Insights into Therapeutics.International journal of molecular sciences · 2023Article
- Small Molecule Cocktails Promote Fibroblast-to-Leydig-like Cell Conversion for Hypogonadism Therapy.Pharmaceutics · 2023Article
- Forward genetic screening using fundus spot scale identifies an essential role for Lipe in murine retinal homeostasis.Communications biology · 2023Article
- Regulation of retinoid mediated StAR transcription and steroidogenesis in hippocampal neuronal cells: Implications for StAR in protecting Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Expression and Function of StAR in Cancerous and Non-Cancerous Human and Mouse Breast Tissues: New Insights into Diagnosis and Treatment of Hormone-Sensitive Breast Cancer.International journal of molecular sciences · 2023Article
- Omega-6 highly unsaturated fatty acids in Leydig cells facilitate male sex hormone production.Communications biology · 2022Article
- Exogenous cholesterol acquisition signaling in LH-responsive MA-10 Leydig cells and in adult mice.The Journal of endocrinology · 2022Article
- Functional metabolite reserves and lipid homeostasis revealed by the MA-10 Leydig cell metabolome.PNAS nexus · 2022Article
- Hormonal and Genetic Regulatory Events in Breast Cancer and Its Therapeutics: Importance of the Steroidogenic Acute Regulatory Protein.Biomedicines · 2022Review
- Xiao-Chai-Hu Decoction Ameliorates Poly (I:C)-Induced Viral Pneumonia through Inhibiting Inflammatory Response and Modulating Serum Metabolism.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Luteinizing Hormone Regulation of Inter-Organelle Communication and Fate of the Corpus Luteum.International journal of molecular sciences · 2021Review
- Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.Molecular and cellular endocrinology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of cholesteryl esters in steroidogenic tissues and, thus, facilitates cholesterol availability for steroidogenesis. The steroidogenic acute regulatory protein (StAR) controls the rate-limiting step in steroid biosynthesis. However, the modes of action of HSL in the regulation of StAR expression remain obscure. We demonstrate in MA-10 mouse Leydig cells that activation of the protein kinase A (PKA) pathway, by a cAMP analog Bt2cAMP, enhanced expression of HSL and its phosphorylation (P) at Ser-660 and Ser-563, but not at Ser-565, concomitant with increased HSL activity. Phosphorylation and activation of HSL coincided with increases in StAR, P-StAR (Ser-194), and progesterone levels. Inhibition of HSL activity by CAY10499 effectively suppressed Bt2cAMP-induced StAR expression and progesterone synthesis. Targeted silencing of endogenous HSL, with siRNAs, resulted in increased cholesteryl ester levels and decreased cholesterol content in MA-10 cells. Depletion of HSL affected lipoprotein-derived cellular cholesterol influx, diminished the supply of cholesterol to the mitochondria, and resulted in the repression of StAR and P-StAR levels. Cells overexpressing HSL increased the efficacy of liver X receptor (LXR) ligands on StAR expression and steroid synthesis, suggesting HSL-mediated steroidogenesis entails enhanced oxysterol production. Conversely, cells deficient in LXRs exhibited decreased HSL responsiveness. Furthermore, an increase in HSL was correlated with the LXR target genes, steroid receptor element-binding protein 1c and ATP binding cassette transporter A1, demonstrating HSL-dependent regulation of steroidogenesis predominantly involves LXR signaling. LXRs interact/cooperate with RXRs and result in the activation of StAR gene transcription. These findings provide novel insight and demonstrate the molecular events by which HSL acts to drive cAMP/PKA-mediated regulation of StAR expression and steroidogenesis in mouse Leydig cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.