{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:22:35Z","timestamp":1789474955702,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Government (MSIT)","award":["2022R1A2C100667511"],"award-info":[{"award-number":["2022R1A2C100667511"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoid receptors (GRs) play a pivotal role in the stress response of the body, but overactivation can disrupt normal physiological functions. This study explores the role of cyclic adenosine monophosphate (cAMP) in GR activation and the associated mechanisms. We initially used the human embryonic kidney 293 cell line (HEK293) and found that cAMP enhancement, using forskolin and 3-isobutyl-1-methylxanthine (IBMX), did not alter glucocorticoid signaling under normal conditions, as evidenced by glucocorticoid response element (GRE) activity and the translocation of GR. However, in stressful conditions induced by dexamethasone, a synthetic glucocorticoid, cAMP was found to lessen glucocorticoid signaling within a short time frame but amplify it over an extended period in HEK293 cells. Bioinformatic analysis revealed that cAMP upregulation triggers the extracellular signal-regulated kinase (ERK) pathway, which influences GR translocation and ultimately regulates its activity. This stress-modulating function of cAMP was also investigated in the Hs68 dermal fibroblast line, known for its susceptibility to glucocorticoids. We found that cAMP enhancement via forskolin reduces GRE activity and reverses collagen loss in Hs68 cells exposed to dexamethasone. These findings underline the context-specific role of cAMP signaling in managing glucocorticoid signaling and its potential therapeutic application in treating stress-related pathological conditions like skin aging characterized by collagen reduction.<\/jats:p>","DOI":"10.3390\/ijms241210180","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Role of Cyclic Adenosine Monophosphate (cAMP) in Modulating Glucocorticoid Receptor Signaling and Its Implications on Glucocorticoid-Related Collagen Loss"],"prefix":"10.3390","volume":"24","author":[{"given":"Wesuk","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dabin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyun","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yearim","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojeong","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhjin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-9407","authenticated-orcid":false,"given":"Taesun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","first-page":"109","article-title":"Glucocorticoids, stress, and fertility","volume":"35","author":"Whirledge","year":"2010","journal-title":"Minerva Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000362736","article-title":"Stress, the stress system and the role of glucocorticoids","volume":"22","author":"Nicolaides","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.mce.2006.12.012","article-title":"Differential expression of HPA axis homolog in the skin","volume":"265","author":"Slominski","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1096\/fasebj.10.14.9002552","article-title":"MIF rediscovered: Cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response","volume":"10","author":"Bucala","year":"1996","journal-title":"FASEB J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/1203475416685077","article-title":"Review of atopic dermatitis and topical therapies","volume":"21","author":"Mayba","year":"2017","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1136\/thorax.55.7.603","article-title":"Molecular mechanisms of glucocorticoid action: What is important?","volume":"55","author":"Newton","year":"2000","journal-title":"Thorax"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Timmermans, S., Vandewalle, J., and Libert, C. (2022). Dimerization of the glucocorticoid receptor and its importance in (patho) physiology: A primer. Cells, 11.","DOI":"10.3390\/cells11040683"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.revmed.2004.01.012","article-title":"Glucocorticoids and their receptor: Mechanisms of action and clinical implications","volume":"25","author":"Roumestan","year":"2004","journal-title":"La Rev. De Med. Interne"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.7150\/ijbs.73915","article-title":"Reversion of glucocorticoid-induced senescence and collagen synthesis decrease by LY294002 is mediated through p38 in skin","volume":"18","author":"Le","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1365-2230.1991.tb01225.x","article-title":"New aspects of the mechanism of corticosteroid\u2013induced dermal atrophy","volume":"16","author":"Oikarinen","year":"1991","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.bbi.2009.06.002","article-title":"Stress, immunity and skin collagen integrity: Evidence from animal models and clinical conditions","volume":"23","author":"Kahan","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1124\/pharmrev.120.000086","article-title":"Subcellular organization of the cAMP signaling pathway","volume":"73","author":"Zaccolo","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"ref_13","first-page":"a011148","article-title":"The cyclic AMP pathway","volume":"4","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2016.00123","article-title":"The cAMP pathway as therapeutic target in autoimmune and inflammatory diseases","volume":"7","author":"Raker","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.abb.2014.07.003","article-title":"Cyclic AMP (cAMP) signaling in melanocytes and melanoma","volume":"563","author":"Setaluri","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.yjmcc.2011.08.016","article-title":"PDEs create local domains of cAMP signaling","volume":"52","author":"Mika","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0955-0674(99)00073-3","article-title":"Regulation of cAMP and cGMP signaling: New phosphodiesterases and new functions","volume":"12","author":"Soderling","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kovanich, D., Low, T.Y., and Zaccolo, M. (2023). Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054667"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hong, K.P., Spitzer, N.C., and Nicol, X. (2011). Improved molecular toolkit for cAMP studies in live cells. BMC Res. Notes, 4.","DOI":"10.1186\/1756-0500-4-241"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3389\/fncel.2014.00376","article-title":"Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits","volume":"8","author":"Averaimo","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1046\/j.0953-816x.2001.01876.x","article-title":"Glucocorticoids interact with the basolateral amygdala \u03b2-adrenoceptor\u2013cAMP\/cAMP\/PKA system in influencing memory consolidation","volume":"15","author":"Roozendaal","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"L345","DOI":"10.1152\/ajplung.00393.2019","article-title":"Budesonide enhances agonist-induced bronchodilation in human small airways by increasing cAMP production in airway smooth muscle","volume":"318","author":"Johnstone","year":"2020","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1600-0773.1989.tb01151.x","article-title":"Studies of glucocorticoid enhancement of the capacity of hepatocytes to accumulate cyclic AMP","volume":"65","author":"Thoresen","year":"1989","journal-title":"Pharmacol. Toxicol."},{"key":"ref_24","first-page":"2","article-title":"Cyclic adenosine monophosphate signaling in inflammatory skin disease","volume":"7","author":"Levy","year":"2016","journal-title":"J. Clin. Exp. Derm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/1744666X.2017.1304820","article-title":"2% Crisaborole topical ointment for the treatment of mild-to-moderate atopic dermatitis","volume":"13","author":"Cheape","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/exd.13808","article-title":"The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition","volume":"28","author":"Hanifin","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nsmb.2022","article-title":"ERK and PDE4 cooperate to induce RAF isoform switching in melanoma","volume":"18","author":"Marquette","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13845","DOI":"10.1073\/pnas.1201917110","article-title":"MC1R and cAMP signaling inhibit cdc25B activity and delay cell cycle progression in melanoma cells","volume":"110","author":"Lyons","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3892\/etm.2012.587","article-title":"Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells","volume":"4","author":"Watanabe","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kang, W., Choi, D., Park, S., and Park, T. (2020). Carvone decreases melanin content by inhibiting melanoma cell proliferation via the cyclic adenosine monophosphate (cAMP) pathway. Molecules, 25.","DOI":"10.3390\/molecules25215191"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Son, B., Kang, W., Park, S., Choi, D., and Park, T. (2021). Dermal olfactory receptor OR51B5 is essential for survival and collagen synthesis in human dermal fibroblast (Hs68 cells). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179273"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Choi, D., Kang, W., Park, S., Son, B., and Park, T. (2021). \u03b2-ionone attenuates dexamethasone-induced suppression of collagen and hyaluronic acid synthesis in human dermal fibroblasts. Biomolecules, 11.","DOI":"10.3390\/biom11050619"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kang, W., Choi, D., and Park, T. (2020). Decanal protects against UVB-induced photoaging in human dermal fibroblasts via the cAMP pathway. Nutrients, 12.","DOI":"10.3390\/nu12051214"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0955-0674(99)00085-X","article-title":"A-kinase anchoring proteins: Protein kinase A and beyond","volume":"12","author":"Edwards","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3389\/fendo.2018.00538","article-title":"The molecular basis for specificity at the level of the protein kinase a catalytic subunit","volume":"9","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.gene.2015.11.052","article-title":"Protein kinase A catalytic subunit isoform PRKACA.; History, function and physiology","volume":"577","author":"Turnham","year":"2016","journal-title":"Gene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0962-8924(02)02294-8","article-title":"Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation","volume":"12","author":"Stork","year":"2002","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10305","DOI":"10.1073\/pnas.90.21.10305","article-title":"Increasing cAMP attenuates activation of mitogen-activated protein kinase","volume":"90","author":"Sevetson","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1006\/cbir.1998.0314","article-title":"Effects of cAMP on ERK mitogen-activated protein kinase activity in hepatocytes do not parallel the bidirectional regulation of DNA synthesis","volume":"23","author":"Thoresen","year":"1999","journal-title":"Cell Biol. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/(SICI)1097-4644(19971201)67:3<353::AID-JCB7>3.0.CO;2-V","article-title":"cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation","volume":"67","author":"Lee","year":"1997","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1046\/j.1523-1755.2000.00991.x","article-title":"cAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway","volume":"57","author":"Yamaguchi","year":"2000","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13957","DOI":"10.1074\/jbc.M006852200","article-title":"The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis","volume":"276","author":"Seger","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1038\/sj.onc.1204632","article-title":"The ERK-dependent signalling is stage-specifically modulated by FSH, during primary Sertoli cell maturation","volume":"20","author":"Marion","year":"2001","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20070797","article-title":"The selectivity of protein kinase inhibitors: A further update","volume":"408","author":"Bain","year":"2007","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1527-3466.2006.00261.x","article-title":"The many faces of H89: A review","volume":"24","author":"Lochner","year":"2006","journal-title":"Cardiovasc. Drug Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kang, W., Choi, D., Son, B., Park, S., and Park, T. (2022). Activation of OR10A3 by Suberic Acid Promotes Collagen Synthesis in UVB-Irradiated Dermal Fibroblasts via the cAMP-Akt Pathway. Cells, 11.","DOI":"10.3390\/cells11243961"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18819","DOI":"10.1074\/jbc.M610537200","article-title":"A novel phosphoinositide 3-kinase-dependent pathway for angiotensin II\/AT-1 receptor-mediated induction of collagen synthesis in MES-13 mesangial cells","volume":"282","author":"Yano","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1159\/000430160","article-title":"The effect of cAMP-PKA activation on TGF-\u03b21-induced profibrotic signaling","volume":"36","author":"Weng","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tao, Y., Pan, M., Liu, S., Fang, F., Lu, R., Lu, C., Zheng, M., An, J., Xu, H., and Zhao, F. (2013). cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071441"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1073\/pnas.0408704102","article-title":"Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase","volume":"102","author":"Swaney","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"L405","DOI":"10.1152\/ajplung.00232.2006","article-title":"Prostaglandin E2 inhibits collagen expression and proliferation in patient-derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling","volume":"292","author":"Huang","year":"2007","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1096\/fj.13-241646","article-title":"Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2\/3","volume":"28","author":"Fernandez","year":"2014","journal-title":"FASEB J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1021\/acs.jmedchem.9b00711","article-title":"Discovery of a Potent Steroidal Glucocorticoid Receptor Antagonist with Enhanced Selectivity against the Progesterone and Androgen Receptors (OP-3633)","volume":"62","author":"Du","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e13572","DOI":"10.1111\/acel.13572","article-title":"Ipriflavone as a non-steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice","volume":"21","author":"Nie","year":"2022","journal-title":"Aging Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S261","DOI":"10.1067\/mai.2002.129705","article-title":"Molecular interactions between glucocorticoids and long-acting \u03b22-agonists","volume":"110","author":"Adcock","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/iub.245","article-title":"Emerging roles of glucocorticoid receptor phosphorylation in modulating glucocorticoid hormone action in health and disease","volume":"61","author":"Cidlowski","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sevilla, L.M., Jim\u00e9nez-Panizo, A., Alegre-Mart\u00ed, A., Est\u00e9banez-Perpi\u00f1\u00e1, E., Caelles, C., and P\u00e9rez, P. (2021). Glucocorticoid resistance: Interference between the glucocorticoid receptor and the MAPK signalling pathways. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810049"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1513\/pats.200402-005MS","article-title":"Mechanisms of glucocorticoid receptor action in noninflammatory and inflammatory cells","volume":"1","author":"Necela","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrm.2016.152","article-title":"Glucocorticoid receptor control of transcription: Precision and plasticity via allostery","volume":"18","author":"Weikum","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"572981","DOI":"10.3389\/fendo.2020.572981","article-title":"Multifaceted control of GR signaling and its impact on hepatic transcriptional networks and metabolism","volume":"11","author":"Correia","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10330","DOI":"10.1073\/pnas.1303635110","article-title":"Kinetics of gene derepression by ERK signaling","volume":"110","author":"Lim","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0248-4900(01)01125-X","article-title":"The Raf\/MEK\/ERK pathway: New concepts of activation","volume":"93","author":"Peyssonnaux","year":"2001","journal-title":"Biol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1073\/pnas.95.5.2050","article-title":"Antagonism of glucocorticoid receptor transcriptional activation by the c-Jun N-terminal kinase","volume":"95","author":"Rogatsky","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1210\/en.2014-1663","article-title":"Synthetic high-density lipoprotein (sHDL) inhibits steroid production in HAC15 adrenal cells","volume":"157","author":"Taylor","year":"2016","journal-title":"Endocrinology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1530\/JOE-10-0493","article-title":"The effects of adrenocorticotrophic hormone on steroid metabolomic profiles in human adrenal cells","volume":"209","author":"Xing","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1001\/archinternmed.2007.41","article-title":"Glucocorticoid receptor gene and risk of cardiovascular disease","volume":"168","author":"Koper","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/oby.2002.146","article-title":"The glucocorticoid receptor gene and its association to metabolic syndrome","volume":"10","author":"Rosmond","year":"2002","journal-title":"Obes. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s100720170016","article-title":"Stress, glucocorticoids and the susceptibility to develop autoimmune disorders of the central nervous system","volume":"22","author":"Morale","year":"2001","journal-title":"Neurol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ejphar.2008.03.012","article-title":"Corticosteroid receptor-gene variants: Modulators of the stress-response and implications for mental health","volume":"585","author":"DeRijk","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:55:40Z","timestamp":1760126140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":70,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms241210180"],"URL":"https:\/\/doi.org\/10.3390\/ijms241210180","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]}}}