Sp1 regulates steroidogenic genes and LHCGR expression in primary human luteinized granulosa cells
Autor: | S.M. Convissar, N. Winston, H. Scoccia, A.M. Zamah, Carlos Stocco, Michelle A. Fierro |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
endocrine system Sp1 Transcription Factor Endocrinology Diabetes and Metabolism Clinical Biochemistry Stimulation Fertilization in Vitro Biology Chorionic Gonadotropin Biochemistry Article Human chorionic gonadotropin 03 medical and health sciences 0302 clinical medicine Endocrinology Luteal Cells medicine Humans Molecular Biology Gene Cells Cultured reproductive and urinary physiology Messenger RNA urogenital system GATA4 Cell Biology Receptors LH Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Molecular Medicine Female Steroids Luteinizing hormone Corpus luteum hormones hormone substitutes and hormone antagonists Hormone |
Zdroj: | J Steroid Biochem Mol Biol |
ISSN: | 0960-0760 |
Popis: | Luteinizing hormone and human chorionic gonadotropin (hCG) bind to the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). LHCGR is required to maintain corpus luteum function but the mechanisms involved in the regulation of LHCGR in human luteal cells remain incompletely understood. This study aimed to characterize the expression of LHCGR mRNA in primary human luteinized granulosa cells (hLGCs) obtained from patients undergoing in vitro fertilization and to correlate LHCGR expression with the response of hLGCs to hCG by assessing the expression of genes known to be markers of hCG actions. The results show that LHCGR expression is low in freshly isolated cells but recovers rapidly in culture and that hCG maintains LHCGR expression, suggesting a positive feedback loop. The activity of a LHCGR-LUC reporter increased in cells treated with hCG but not with follicle-stimulating hormone. Treatment with hCG also stimulated the expression of genes involved in steroidogenesis in a time-dependent manner. LHCGR promoter expression was found to be regulated by SP1, which we show is highly expressed in hLGCs. Moreover, SP1 inhibition prevented the stimulation of steroidogenic genes and the increase in LHCGR-LUC reporter activity by hCG. Finally, we provide evidence that a complex formed by SP1 and GATA4 may play a role in the maintenance of LHCGR expression. This report reveals the mechanisms involved in the regulation of the LHCGR and provides experimental data demonstrating that the proximal region of the LHCGR promoter is sufficient to drive the expression of this gene in primary hLGCs. |
Databáze: | OpenAIRE |
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