المؤلفون: Marie-Charlotte Meinsohn, Kalyne Bertolin, Olivia Eilers Smith, Bruce D. Murphy

المصدر: Physiological Reviews. 99:1249-1279

مصطلحات موضوعية: Male, 0301 basic medicine, Steroidogenic factor 1, endocrine system, Protein Conformation, Physiology, Endometriosis, Receptors, Cytoplasmic and Nuclear, Breast Neoplasms, Biology, Ligands, Steroidogenic Factor 1, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Testicular Neoplasms, Pregnancy, Physiology (medical), Animals, Humans, Receptor, Molecular Biology, Transcription factor, Ovarian Neoplasms, Regulation of gene expression, Reproduction, Liver receptor homolog-1, General Medicine, Cell biology, 030104 developmental biology, Gene Expression Regulation, Nuclear receptor, 030220 oncology & carcinogenesis, Female, Signal transduction, Leydig Cell Tumor, Signal Transduction

الوصف: Nuclear receptors are intracellular proteins that act as transcription factors. Proteins with classic nuclear receptor domain structure lacking identified signaling ligands are designated orphan nuclear receptors. Two of these, steroidogenic factor-1 (NR5A1, also known as SF-1) and liver receptor homolog-1 (NR5A2, also known as LRH-1), bind to the same DNA sequences, with different and nonoverlapping effects on targets. Endogenous regulation of both is achieved predominantly by cofactor interactions. SF-1 is expressed primarily in steroidogenic tissues, LRH-1 in tissues of endodermal origin and the gonads. Both receptors modulate cholesterol homeostasis, steroidogenesis, tissue-specific cell proliferation, and stem cell pluripotency. LRH-1 is essential for development beyond gastrulation and SF-1 for genesis of the adrenal, sexual differentiation, and Leydig cell function. Ovary-specific depletion of SF-1 disrupts follicle development, while LRH-1 depletion prevents ovulation, cumulus expansion, and luteinization. Uterine depletion of LRH-1 compromises decidualization and pregnancy. In humans, SF-1 is present in endometriotic tissue, where it regulates estrogen synthesis. SF-1 is underexpressed in ovarian cancer cells and overexpressed in Leydig cell tumors. In breast cancer cells, proliferation, migration and invasion, and chemotherapy resistance are regulated by LRH-1. In conclusion, the NR5A orphan nuclear receptors are nonredundant factors that are crucial regulators of a panoply of biological processes, across multiple reproductive tissues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::618135015cc960f4266d35ab18f48deeTest
https://doi.org/10.1152/physrev.00019.2018Test

المؤلفون: Anthony Daniel Bird, Andrew H. Sinclair, Vincent R. Harley, Brittany Croft, Faustine Declosmenil, Peter Koopman, Louisa Mabel Ludbrook, Francis Poulat, Ken McElreavey, Kevin Christopher Knower, Brett Daniel Fisher, Janelle Ryan, Anu Bashamboo, Rajini Sreenivasan

المساهمون: University of Melbourne, Monash University [Victoria, Australia], Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hudson Institute of Medical Research [Clayton], Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP), Murdoch Children’s Research Institute [Melbourne, Australia], Institute for Molecular Bioscience, University of Queensland [Brisbane], This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Program Grants 334314 and 546517 to V.H., P.K., and A.S. and by the Victorian Government's Operational Infrastructure Support Program (OIS). R.S. was supported by an Australian Postgraduate Award. B.C. is supported by an Australian Government Research Training Program Scholarship, through Monash University. V.H., P.K.. and A.S. are supported by NHMRC Research Fellowships.

المصدر: Human Mutation
Human Mutation, 2018, 39 (12), pp.1861-1874. ⟨10.1002/humu.23603⟩

مصطلحات موضوعية: Male, 0301 basic medicine, Steroidogenic factor 1, MESH: Sequence Analysis, DNA, testis-specific enhancer of SOX9, Mutant, sex determination, DSD, Ligands, Steroidogenic Factor 1, medicine.disease_cause, 0302 clinical medicine, MESH: Child, MESH: Ligands, Disorders of sex development, Child, Genetics (clinical), Regulation of gene expression, Genetics, Mutation, MESH: Infant, Newborn, MESH: Disorder of Sex Development, 46,XY, SOX9 Transcription Factor, MESH: Infant, MESH: Gene Expression Regulation, Enhancer Elements, Genetic, Testis determining factor, MESH: HEK293 Cells, Child, Preschool, SF-1, SOX9, Protein Binding, Adult, MESH: Mutation, Adolescent, 030209 endocrinology & metabolism, Biology, MESH: SOX9 Transcription Factor, 03 medical and health sciences, MESH: Computer Simulation, medicine, MESH: Protein Binding, Humans, Computer Simulation, Enhancer, MESH: Adolescent, MESH: Humans, Disorder of Sex Development, 46,XY, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Adult, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Sequence Analysis, DNA, MESH: Steroidogenic Factor 1, medicine.disease, MESH: Male, HEK293 Cells, 030104 developmental biology, Gene Expression Regulation, MESH: Enhancer Elements, Genetic

الوصف: International audience; Nuclear receptor subfamily 5 group A member 1/Steroidogenic factor 1 (NR5A1; SF-1; Ad4BP) mutations cause 46,XY disorders of sex development (DSD), with phenotypes ranging from developmentally mild (e.g., hypospadias) to severe (e.g., complete gonadal dysgenesis). The molecular mechanism underlying this spectrum is unclear. During sex determination, SF-1 regulates SOX9 (SRY [sex determining region Y]-box 9) expression. We hypothesized that SF-1 mutations in 46,XY DSD patients affect SOX9 expression via the Testis-specific Enhancer of Sox9 core element, TESCO. Our objective was to assess the ability of 20 SF-1 mutants found in 46,XY DSD patients to activate TESCO. Patient DNA was sequenced for SF-1 mutations and mutant SF-1 proteins were examined for transcriptional activity, protein expression, sub-cellular localization and in silico structural defects. Fifteen of the 20 mutants showed reduced SF-1 activation on TESCO, 11 with atypical sub-cellular localization. Fourteen SF-1 mutants were predicted in silico to alter DNA, ligand or cofactor interactions. Our study may implicate aberrant SF-1-mediated transcriptional regulation of SOX9 in 46,XY DSDs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85bf3bb6c1222048f9bebd0d6dd26b0bTest
https://doi.org/10.1002/humu.23603Test

المؤلفون: Fangxi Zhang, Lijun Ding, Guijun Yan, Fei Yu, Hongjie Pan, Yifan Li, Lingling Zhang, Runsheng Li, Yanhong Xu, Xiaofeng Wan

المصدر: Life sciences. 278

مصطلحات موضوعية: 0301 basic medicine, Male, endocrine system, Chromatin Immunoprecipitation, Endocytosis, Exosomes, Steroidogenic Factor 1, 030226 pharmacology & pharmacy, Clathrin, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Animals, Testosterone, General Pharmacology, Toxicology and Pharmaceutics, RNA, Small Interfering, Promoter Regions, Genetic, Regulation of gene expression, Mice, Knockout, Gene knockdown, biology, Chemistry, Gene targeting, Leydig Cells, General Medicine, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Gene Expression Regulation, Knockout mouse, biology.protein, Female, CRISPR-Cas Systems, Carrier Proteins, Chromatin immunoprecipitation, Plasmids

الوصف: Aims Increasing evidence has shown that hormone secretion is regulated by endocytosis. Eps15 homology domain-containing protein 3 (EHD3) is an endocytic-trafficking regulatory protein, but whether EHD3 is associated with testosterone secretion is not clear. This work aims to explore the role of EHD3 in testosterone synthesis. Main methods Testosterone concentration was determined by ELISA. The effects of EHD3 on endocytosis were assessed by exosomes tracing assay and Immunofluorescence. Targeting relationship between EHD3 and NR5A1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assay in Leydig cells. For in vivo assessments, conditional NR5A1 knockout mouse model was established with CRISPR/Cas9 gene targeting technology. Key findings EHD3 overexpression significantly increased the concentration of testosterone. EHD3 knockdown markedly decreased testosterone synthesis by reducing endocytosis. The activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence “AGGTCA” in the EHD3 promoter. Furthermore, mice with a Leydig cell-specific conditional NR5A1 knockout displayed the blunted levels of EHD3 and clathrin (a key factor for endocytosis), and serum testosterone concentration compared with NR5A1f/f mice. Significance This study suggests a potential molecular mechanism of testosterone synthesis to fully understand male reproductive health.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97d1b6935a684bde974441f12ab56f40Test
https://pubmed.ncbi.nlm.nih.gov/33964295Test

المؤلفون: Zhiyuan Zhang, Hua Huang, Xiaoyu Xing, Xiangyu Zou, Liang Zhong, Jin Zhou, Yanping Hou, Jie Sun

المصدر: Journal of Cellular and Molecular Medicine

مصطلحات موضوعية: 0301 basic medicine, Male, Transcriptional Activation, endocrine system, gene activation, Foreskin, Endogeny, Biology, Steroidogenic Factor 1, Chorionic Gonadotropin, Human chorionic gonadotropin, Cell Line, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Testosterone, Regulation of gene expression, Leydig cell, induced Leydig cells, male hypogonadism, reprogramming, Leydig Cells, Cell Biology, Original Articles, Fibroblasts, Cellular Reprogramming, Cell biology, GATA4 Transcription Factor, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Cell culture, 030220 oncology & carcinogenesis, human foreskin fibroblasts, Molecular Medicine, Original Article, CRISPR-Cas Systems, Reprogramming, CRISPR‐Cas9, RNA, Guide, Kinetoplastida, Transcription Factors

الوصف: Recently, Leydig cell (LC) transplantation has been revealed as a promising strategy for treating male hypogonadism; however, the key problem restricting the application of LC transplantation is a severe lack of seed cells. It seems that targeted activation of endogenous genes may provide a potential alternative. Therefore, the aim of this study was to determine whether targeted activation of Nr5a1, Gata4 and Dmrt1 (NGD) via the CRISPR/dCas9 synergistic activation mediator system could convert human foreskin fibroblasts (HFFs) into functional Leydig‐like cells. We first constructed the stable Hsd3b‐dCas9‐MPH‐HFF cell line using the Hsd3b‐EGFP, dCas9‐VP64 and MS2‐P65‐HSF1 lentiviral vectors and then infected it with single guide RNAs. Next, we evaluated the reprogrammed cells for their reprogramming efficiency, testosterone production characteristics and expression levels of Leydig steroidogenic markers by quantitative real‐time polymerase chain reaction or Western blotting. Our results showed that the reprogramming efficiency was close to 10% and that the reprogrammed Leydig‐like cells secreted testosterone rapidly and, more importantly, responded effectively to stimulation with human chorionic gonadotropin and expressed Leydig steroidogenic markers. Our findings demonstrate that simultaneous targeted activation of the endogenous NGD genes directly reprograms HFFs into functional Leydig‐like cells, providing an innovative technology that may have promising potential for the treatment of male androgen deficiency diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b2c24b032005e1efa1e815559c9e70bTest
http://europepmc.org/articles/PMC6714237Test

المؤلفون: Monica M. França, Antonio M. Lerario, Maria Candida Barisson Villares Fragoso, Claudimara Ferini Pacicco Lotfi

المصدر: Clinics
Clinics, Vol 72, Iss 6, Pp 391-394
Clinics; v. 72 n. 6 (2017); 391-394
Clinics; Vol. 72 Núm. 6 (2017); 391-394
Clinics; Vol. 72 No. 6 (2017); 391-394
Universidade de São Paulo (USP)
instacron:USP
Clinics, Volume: 72, Issue: 6, Pages: 391-394, Published: JUN 2017

مصطلحات موضوعية: Steroidogenic factor 1, Small interfering RNA, POD1, Blotting, Western, Immunoblotting, Down-Regulation, Biology, Real-Time Polymerase Chain Reaction, Steroidogenic Factor 1, siRNA-POD1, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Gene expression, Basic Helix-Loop-Helix Transcription Factors, medicine, Humans, Adrenocortical carcinoma, Gene silencing, Transcription factor, TCF21, Regulation of gene expression, lcsh:R5-920, Gene knockdown, Adrenocortical Tumor Cells, General Medicine, medicine.disease, Adrenal Cortex Neoplasms, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Cancer research, SF-1, lcsh:Medicine (General), Rapid Communication, 030215 immunology

الوصف: OBJECTIVES: Transcription Factor 21 represses steroidogenic factor 1, a nuclear receptor required for gonadal development, sex determination and the regulation of adrenogonadal steroidogenesis. The aim of this study was to investigate whether silencing or overexpression of the gene Transcription Factor 21 could modulate the gene and protein expression of steroidogenic factor 1 in adrenocortical tumors. METHODS: We analyzed the gene expression of steroidogenic factor 1 using qPCR after silencing endogenous Transcription Factor 21 in pediatric adrenal adenoma-T7 cells through small interfering RNA. In addition, using overexpression of Transcription Factor 21 in human adrenocortical carcinoma cells, we analyzed the protein expression of steroidogenic factor 1 using Western blotting. RESULTS: Transcription Factor 21 knockdown increased the mRNA expression of steroidogenic factor 1 by 5.97-fold in pediatric adrenal adenoma-T7 cells. Additionally, Transcription Factor 21 overexpression inhibited the protein expression of steroidogenic factor 1 by 0.41-fold and 0.64-fold in two different adult adrenocortical carcinoma cell cultures, H295R and T36, respectively. CONCLUSIONS: Transcription Factor 21 is downregulated in adrenocortical carcinoma cells. Taken together, these findings support the hypothesis that Transcription Factor 21 is a regulator of steroidogenic factor 1 and is a tumor suppressor gene in pediatric and adult adrenocortical tumors.

وصف الملف: application/pdf; text/html

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3eb32e59f48fb1af860b84868c64caadTest
https://doi.org/10.6061/clinics/2017Test(06)10

المؤلفون: Jagadeesan Arunakaran, T. Sathish Kumar, S. Balakrishnan, E. Sugantha Priya, P. Raja Singh

المصدر: Reproductive Sciences. 25:818-829

مصطلحات موضوعية: 0301 basic medicine, Steroidogenic factor 1, Regulation of gene expression, endocrine system, Methyltransferase, Obstetrics and Gynecology, Methylation, Biology, Cell biology, Toxicology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, DNA methylation, Gene expression, Epigenetics, Transcription factor, 030217 neurology & neurosurgery

الوصف: Polychlorinated biphenyl (PCB) is an endocrine-disrupting chemical. Sertoli cells (SCs) provide physical and nutritional support for developing germ cells. Dysfunction in SCs has adverse effects on spermatogenesis. Previously, we found that the lactational exposure of PCBs (1, 2, and 5 mg/kg birth weight/day, orally from postnatal days 1 to 20) decreased the follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) expression in SCs of F1 progeny. Transcription factors initiate and regulate the transcription of genes. DNA methylation plays an important role in epigenetic gene regulation. Hence, this study was aimed to identify the level of transcription factors regulating FSHR, AR gene expression, and DNA methylation in the promoter of these genes in SCs of both F1 prepuberal and puberal offspring. DNA methylation in the promoter of FSHR and AR genes was examined by sodium bisulfite conversion technique. The protein levels of transcription factors (steroidogenic factor 1 [SF1], upstream stimulatory factors 1 and 2, c-fos, c-jun, and CREB-binding protein) and enzymes DNA methyltransferases (Dnmt1, Dnmt3ab, Dnmt3l, and histone deacetylase 1 [HDAC1]) were analyzed by Western blotting. The transcription factors that regulate the FSHR and AR gene in SCs were decreased in both the PCB-exposed F1 progeny. Methylation was observed in the promoter of FSHR, AR, and SF1. The protein levels of Dnmt1, Dnmt3ab, Dnmt3l, and HDAC1 were increased in the PCBs-treated groups. Subsequently, it leads to transcriptional repression of the genes in SCs. Our finding suggests that PCBs caused epigenetic change in SCs, thereby it impaired SCs function in F1 progeny.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::022cc19e7c3bdb5a237a42a7d7f21682Test
https://doi.org/10.1177/1933719117699707Test

المؤلفون: Marie France Bouchard, Francis Bergeron, Jasmine Grenier Delaney, Louis-Mathieu Harvey, Robert S Viger

المصدر: Endocrinology. 160(4)

مصطلحات موضوعية: 0301 basic medicine, Steroidogenic factor 1, Anti-Mullerian Hormone, Male, medicine.medical_specialty, endocrine system, Sex Differentiation, HMG-box, endocrine system diseases, 030209 endocrinology & metabolism, SOX9, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Internal medicine, Testis, medicine, Transcriptional regulation, Animals, Promoter Regions, Genetic, Transcription factor, Research Articles, Regulation of gene expression, Messenger RNA, GATA4, urogenital system, Ovary, Gene Expression Regulation, Developmental, GATA4 Transcription Factor, 030104 developmental biology, embryonic structures, Female, hormones, hormone substitutes, and hormone antagonists

الوصف: GATA4 is an essential transcriptional regulator required for gonadal development, differentiation, and function. In the developing testis, proposed GATA4-regulated genes include steroidogenic factor 1 (Nr5a1), SRY-related HMG box 9 (Sox9), and anti-Müllerian hormone (Amh). Although some of these genes have been validated as genuine GATA4 targets, it remains unclear whether GATA4 is a direct regulator of endogenous Amh transcription. We used a CRISPR/Cas9-based approach to specifically inactivate or delete the sole GATA-binding motif of the proximal mouse Amh promoter. AMH mRNA and protein levels were assessed at developmental time points corresponding to elevated AMH levels: fetal and neonate testes in males and adult ovaries in females. In males, loss of GATA binding to the Amh promoter significantly reduced Amh expression. Although the loss of GATA binding did not block the initiation of Amh transcription, AMH mRNA and protein levels failed to upregulate in the developing fetal and neonate testis. Interestingly, adult male mice presented no anatomical anomalies and had no evidence of retained Müllerian duct structures, suggesting that AMH levels, although markedly reduced, were sufficient to masculinize the male embryo. In contrast to males, GATA binding to the Amh promoter was dispensable for Amh expression in the adult ovary. These results provide conclusive evidence that in males, GATA4 is a positive modulator of Amh expression that works in concert with other key transcription factors to ensure that the Amh gene is sufficiently expressed in a correct spatiotemporal manner during fetal and prepubertal testis development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::338b9031ffb9a67e0410dcc8154426c2Test
https://pubmed.ncbi.nlm.nih.gov/30759208Test

المؤلفون: Scott F. Cummins, Abigail Elizur, Prasert Sobhon, Tipsuda Thongbuakaew, Prapee Sretarugsa, Tanapan Siangcham, Saowaros Suwansa-ard

المصدر: Steroids. 107:149-160

مصطلحات موضوعية: 0301 basic medicine, Steroidogenic factor 1, medicine.medical_specialty, medicine.medical_treatment, Clinical Biochemistry, Steroid biosynthesis, Biochemistry, Arthropod Proteins, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Animals, Estrogen Sulfotransferase, Receptor, Molecular Biology, Progesterone, Pharmacology, Regulation of gene expression, Estradiol, biology, Macrobrachium rosenbergii, Organic Chemistry, biology.organism_classification, Cell biology, Steroid hormone, 030104 developmental biology, Gene Expression Regulation, Prawn, Female, Palaemonidae, 030217 neurology & neurosurgery

الوصف: The giant freshwater prawn, Macrobrachium rosenbergii, is important to many Asian countries due to its high economic value as an aquaculture product. With demand increasing, there is requirement for a better understanding of the biosynthetic components that regulate its growth and reproduction, including steroids, in order to help increase production. Vertebrate-type steroids and their receptors were identified in crustaceans and implicated in reproduction. In this study, we presented the sex steroids estradiol and progesterone by LC-MS/MS in female M. rosenbergii, and reveal steroidogenic-related genes by in silico analysis of de novo assembled transcriptomes. Comparative analysis with other species was performed to confirm their putative role, as well as tissue-specific and quantitative gene expression. We reveal 29 transcripts that encode for steroidogenic-related proteins, including steroidogenic enzymes, a nuclear steroid hormone receptors, and a steroidogenic factor. Moreover, we identified for the first time the presence of steroidogenic factor 1, StAR-related lipid transfer protein, estradiol receptor- and progesterone-like protein in M. rosenbergii. Those targeted for gene expression analysis (3 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase, estrogen sulfotransferase and progesterone receptor-like) showed widespread expression within many tissues, and at relatively high levels in the central nervous system (CNS) during ovarian maturation. In summary, we provide further evidence for the existence of steroidogenic pathways in crustaceans, which may be useful for advancing prawn aquaculture.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::242d983933541d136fa613d98e0064ddTest
https://doi.org/10.1016/j.steroids.2016.01.006Test

المؤلفون: Stavros Sifakis, Demetrios A. Spandidos, Ourania Koukoura

المصدر: Molecular Medicine Reports

مصطلحات موضوعية: 0301 basic medicine, endometriosis, Cancer Research, Endometriosis, Bioinformatics, Steroidogenic Factor 1, Biochemistry, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Aromatase, Genetics, medicine, Humans, Genetic Predisposition to Disease, Epigenetics, DNA (Cytosine-5-)-Methyltransferases, Molecular Targeted Therapy, Molecular Biology, Regulation of gene expression, Homeodomain Proteins, 030219 obstetrics & reproductive medicine, DNA methylation, biology, epigenetics, Cancer, pelvic pain, Articles, Cell cycle, medicine.disease, Molecular medicine, 030104 developmental biology, Cell Transformation, Neoplastic, Homeobox A10 Proteins, Oncology, Gene Expression Regulation, Receptors, Estrogen, biology.protein, Molecular Medicine, Female, Receptors, Progesterone, Genome-Wide Association Study

الوصف: Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83c0e715ddac4e44e69a8b8bf94fd11dTest
http://europepmc.org/articles/PMC4805102Test

المؤلفون: Amanda Swain, Yuichi Shima, Jennifer R. Gardiner, Ken Ichirou Morohashi

المصدر: Molecular and Cellular Endocrinology. 351:12-18

مصطلحات موضوعية: Steroidogenic factor 1, Genetically modified mouse, medicine.medical_specialty, Adrenal Gland Neoplasms, Organogenesis, Biology, Steroidogenic Factor 1, Biochemistry, Endocrinology, Transcription (biology), Internal medicine, Adrenal Glands, Transcriptional regulation, medicine, Animals, Humans, Molecular Biology, Transcription factor, Regulation of gene expression, Hyperplasia, medicine.disease, Introns, Neoplasm Proteins, Cell biology, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Enhancer Elements, Genetic

الوصف: SF-1 is a master regulator of steroidogenesis whose expression is critical for normal adrenal and gonadal organogenesis. Strict maintenance of SF-1 levels is essential, and mutations causing under- or overexpression result in congenital adrenal and gonadal defects or hyperplasia, respectively. Data from transgenic mouse models points to a network of transcription factors responsible for stringent regulation of Sf-1 expression during development, which bind to intronic enhancer elements in addition to the basal promoter to specifically modulate transcription in each Sf-1-expressing tissue. Furthermore, analysis of the role of SF-1 in adrenal tumourigenesis implies that improper developmental regulation of Sf-1 expression may have postnatal consequences separate from the well-documented developmental defects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd058b8f948fd4e991c579cfd541b5ddTest
https://doi.org/10.1016/j.mce.2011.10.007Test