{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:19:53Z","timestamp":1761718793010,"version":"build-2065373602"},"reference-count":51,"publisher":"CSIRO Publishing","issue":"3","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":1580,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,4]]},"abstract":"<jats:p>Previous studies demonstrated that progesterone (P4) can promote prostaglandin (PG) E2 production; however, how P4 mediates the synthesis of PGE2 remains unclear. In this study, cervical epithelial cells from mice during the follicular phase were cultured in\u00a0vitro and treated with different concentrations of P4 (5, 10, and 20\u00a0nM). The results of the present study suggest that treatment of murine cervical epithelial cells with 10\u00a0nM P4 for 24\u00a0h contributed to: (1) significantly increased expression of protein kinase A (PKA), cytosolic phospholipase A2 (cPLA2) and PGE synthase (PGES)-1; (2) higher phosphorylated (p-) to total extracellular signal-regulated kinase (ERK) 1\/2 and hormone-sensitive lipase (HSL) ratios; (3) a significant decrease in the number of lipid droplets (LDs) and fatty acid content within LDs in epithelial cells; and (4) enhanced arachidonic acid and PGE2 levels in cells compared with the control (0\u00a0nM P4) group (P\u00a0&amp;lt;\u00a00.01 for all findings). In contrast, the PKA inhibitor H89 contributed to significantly decreased cPLA2, PGES-1 and HSL expression, ERK1\/2 phosphorylation and arachidonic acid and PGE2 levels, even in the presence of P4. These data show that P4 can act via the PKA\/ERK1\/2 pathway to stimulate lipolysis of triacylglycerol in the LD core and degradation of phospholipid in the LD membrane to promote PGE2 synthesis in murine cervical epithelial cells.<\/jats:p>","DOI":"10.1071\/rd20195","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T20:00:21Z","timestamp":1611777621000},"page":"209-219","source":"Crossref","is-referenced-by-count":2,"title":["Effects of progesterone on the lipolysis of lipid droplets and prostaglandin E2 synthesis in murine cervical epithelial cells"],"prefix":"10.1071","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9069-8435","authenticated-orcid":true,"given":"Hongyan","family":"Zhang","sequence":"first","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Su","sequence":"additional","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libo","family":"Huang","sequence":"additional","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boyu","family":"Li","sequence":"additional","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejun","family":"Yuan","sequence":"additional","affiliation":[{"name":"BCollege of Life Science, Shandong Agricultural University, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-8358","authenticated-orcid":true,"given":"Mingjiu","family":"Luo","sequence":"additional","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."},{"name":"CCorresponding authors. Email: glj@sdau.edu.cn; luo9616@163.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4264-2266","authenticated-orcid":true,"given":"Lijiang","family":"Ge","sequence":"additional","affiliation":[{"name":"ACollege of Animal Science and Technology, No. 61 Daizong Street, Taian, Shandong Province, 271018, PR China."},{"name":"CCorresponding authors. Email: glj@sdau.edu.cn; luo9616@163.com"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"67","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"2025102820132677200_R1","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1158\/0008-5472.CAN-07-1999","article-title":"Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells.","volume":"68","author":"Accioly","year":"2008","journal-title":"Cancer Res."},{"key":"2025102820132677200_R2","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1194\/JLR.M600489-JLR200","article-title":"Endothelial cell\u2013pericyte co-cultures induce PLA2 protein expression through activation of PKCa and the MAPK\/ERK cascade.","volume":"48","author":"Anfuso","year":"2007","journal-title":"J. Lipid Res."},{"key":"2025102820132677200_R3","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1095\/BIOLREPROD54.2.371","article-title":"Influence of sex steroids on the production of prostaglandins F2\u03b1 and E2 and response to oxytocin in cultured epithelial and stromal cells of the bovine endometrium.","volume":"54","author":"Asselin","year":"1996","journal-title":"Biol. Reprod."},{"key":"2025102820132677200_R5","doi-asserted-by":"publisher","DOI":"10.1111\/ECI.13017","article-title":"Energy metabolism of white adipose tissue and insulin resistance in humans.","volume":"48","author":"B\u00f3dis","year":"2018","journal-title":"Eur. J. Clin. Invest."},{"key":"2025102820132677200_R4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy.","volume":"224","author":"Bolte","year":"2006","journal-title":"J. Microsc."},{"key":"2025102820132677200_R6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1054\/PLEF.2001.0264","article-title":"Arachidonyl trifluoromethyl ketone induces lipid body formation in leukocytes.","volume":"64","author":"Bozza","year":"2001","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2025102820132677200_R7","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1084\/JEM.186.6.909","article-title":"Eosinophil lipid bodies: specific, inducible intracellular sites for enhanced eicosanoid formation.","volume":"186","author":"Bozza","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025102820132677200_R8","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/J.PLEFA.2011.04.020","article-title":"Lipid body function in eicosanoid synthesis: an update.","volume":"85","author":"Bozza","year":"2011","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"2025102820132677200_R9","doi-asserted-by":"publisher","first-page":"919","DOI":"10.2527\/JAS1973.365919X","article-title":"Control by progesterone of the concentration of lipid droplets in epithelial cells of the sheep endometrium.","volume":"36","author":"Brinsfield","year":"1973","journal-title":"J. Anim. Sci."},{"key":"2025102820132677200_R10","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1007\/BF01928178","article-title":"Lipid droplets of neuroepithelial cells are a major calcium storage site during neural tube formation in chick and mouse embryos.","volume":"48","author":"Bush","year":"1992","journal-title":"Experientia"},{"key":"2025102820132677200_R11","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0035538","article-title":"Mouse estrous cycle identification tool and images.","volume":"7","author":"Byers","year":"2012","journal-title":"PLoS One"},{"key":"2025102820132677200_R12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/35065000","article-title":"Mammalian MAP kinase signalling cascades.","volume":"410","author":"Chang","year":"2001","journal-title":"Nature"},{"key":"2025102820132677200_R13","doi-asserted-by":"publisher","first-page":"5011","DOI":"10.1074\/JBC.275.7.5011","article-title":"Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes.","volume":"275","author":"Clifford","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025102820132677200_R14","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/S10911-017-9386-7","article-title":"Lipid droplet fusion in mammary epithelial cells is regulated by phosphatidylethanolamine metabolism.","volume":"22","author":"Cohen","year":"2017","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"2025102820132677200_R15","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/S0022-2275(20)38034-2","article-title":"Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cell.","volume":"23","author":"Cook","year":"1982","journal-title":"J. Lipid Res."},{"key":"2025102820132677200_R16","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/J.PROSTAGLANDINS.2005.02.001","article-title":"Non-genomic effect of steroids on oxytocin-stimulated intracellular mobilisation of calcium and on prostaglandin F2\u03b1 and E2 secretion from bovine endometrial cells.","volume":"76","author":"Duras","year":"2005","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"2025102820132677200_R17","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1002\/JCP.25978","article-title":"An improved method for primary culture of normal cervical epithelial cells and establishment of cell model in\u00a0vitro with HPV-16 E6 gene by lentivirus.","volume":"233","author":"Fan","year":"2018","journal-title":"J Cell Physiol."},{"key":"2025102820132677200_R18","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/J.CELL.2009.11.005","article-title":"Lipid droplets finally get a little R-E-S-P-E-C-T.","volume":"139","author":"Farese","year":"2009","journal-title":"Cell"},{"key":"2025102820132677200_R19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/S12522-012-0137-6","article-title":"Progesterone-enhanced sperm hyperactivation through IP3\u2013PKC and PKA signals.","volume":"12","author":"Fujinoki","year":"2013","journal-title":"Reprod. Med. Biol."},{"key":"2025102820132677200_R20","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/J.TEM.2017.05.006","article-title":"Progesterone-mediated non-classical signaling.","volume":"28","author":"Garg","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"2025102820132677200_R21","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1095\/BIOLREPROD.111.096040","article-title":"Immunolocalization of adipocytes and prostaglandin E2 and Its four receptor proteins EP1, EP2, EP3, and EP4 in the caprine cervix during spontaneous term labor.","volume":"86","author":"Gu","year":"2012","journal-title":"Biol. Reprod."},{"key":"2025102820132677200_R22","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/J.MCE.2011.09.016","article-title":"Progesterone receptors, their isoforms and progesterone regulated transcription.","volume":"357","author":"Jacobsen","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"2025102820132677200_R23","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1210\/ME.2005-0243","article-title":"Progesterone signalling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term.","volume":"20","author":"Karteris","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"2025102820132677200_R24","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1194\/JLR.R000034","article-title":"Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins.","volume":"51","author":"Kimmel","year":"2010","journal-title":"J. Lipid Res."},{"key":"2025102820132677200_R25","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1071\/RD14490","article-title":"Genomic and non-genomic effects of progesterone on prostaglandin (PG) F2\u03b1 and PGE2 production in the bovine endometrium.","volume":"28","author":"Kuse","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"2025102820132677200_R26","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1210\/ME.2003-0331","article-title":"Making sense of cross-talk between steroid hormone receptors and intracellular signalling pathways: who will have the last word?","volume":"18","author":"Lange","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"2025102820132677200_R27","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1177\/153537020222701104","article-title":"Mechanism of action of progesterone antagonists.","volume":"227","author":"Leonhardt","year":"2002","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"2025102820132677200_R28","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1055\/S-0032-1306343","article-title":"Convergence of multiple mechanisms of steroid hormone action.","volume":"44","author":"Mani","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"2025102820132677200_R29","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/NRM1912","article-title":"Lipid droplets: a unified view of a dynamic organelle.","volume":"7","author":"Martin","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2025102820132677200_R30","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/J.BBALIP.2009.01.003","article-title":"Cytosolic phospholipase A2-driven PGE2 synthesis within unsaturated fatty acids-induced lipid bodies of epithelial cells.","volume":"1791","author":"Moreira","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2025102820132677200_R31","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/J.BBALIP.2017.11.009","article-title":"Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.","volume":"1863","author":"Morel","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"2025102820132677200_R32","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/J.JSBMB.2013.08.011","article-title":"Genomic and non-genomic actions of progestogens in the breast.","volume":"142","author":"Mueck","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2025102820132677200_R33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0090-6980(88)90099-8","article-title":"Effects of estradiol-17 beta and progesterone on the synthesis of prostaglandin F2 alpha, prostaglandin E2 and prostaglandin I2 by fibroblasts from human endometrium in\u00a0vitro.","volume":"36","author":"Neulen","year":"1988","journal-title":"Prostaglandins"},{"key":"2025102820132677200_R34","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/J.DOMANIEND.2017.12.001","article-title":"Effect of fish oil on agonist-induced receptor internalization of the PGF2\u03b1 receptor and cell signaling in bovine luteal cells in\u00a0vitro.","volume":"63","author":"Plewes","year":"2018","journal-title":"Domest. Anim. Endocrinol."},{"key":"2025102820132677200_R35","doi-asserted-by":"publisher","DOI":"10.21769\/BIOPROTOC.1912","article-title":"BODIPY 493\/503 staining of neutral lipid droplets for microscopy and quantification by flow cytometry.","volume":"6","author":"Qiu","year":"2016","journal-title":"Bio Protoc."},{"key":"2025102820132677200_R36","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/J.PHRS.2012.04.005","article-title":"ERK1\/2 MAP kinases: structure, function, and regulation.","volume":"66","author":"Roskoski","year":"2012","journal-title":"Pharmacol. Res."},{"key":"2025102820132677200_R37","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/J.BBALIP.2006.07.011","article-title":"The phospholipase A2 superfamily and its group numbering system.","volume":"1761","author":"Schaloske","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"2025102820132677200_R38","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/J.JSBMB.2014.11.017","article-title":"Progesterone-induced down-regulation of hormone sensitive lipase (Lipe) and up-regulation of G0\/G1 switch 2 (G0s2) genes expression in inguinal adipose tissue of female rats is reflected by diminished rate of lipolysis.","volume":"147","author":"Stelmanska","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2025102820132677200_R39","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1083\/JCB.200210169","article-title":"Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation.","volume":"161","author":"Sztalryd","year":"2003","journal-title":"J. Cell Biol."},{"key":"2025102820132677200_R40","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/J.PROSTAGLANDINS.2016.05.002","article-title":"A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.","volume":"123","author":"Tamura","year":"2016","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"2025102820132677200_R41","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1071\/RD19425","article-title":"Characteristics of lipid droplets and the expression of proteins involved in lipolysis in the murine cervix during mid-pregnancy.","volume":"32","author":"Tao","year":"2020","journal-title":"Reprod. Fertil. Dev."},{"key":"2025102820132677200_R42","doi-asserted-by":"publisher","first-page":"44507","DOI":"10.1074\/JBC.M207712200","article-title":"The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.","volume":"277","author":"Tauchi-Sato","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2025102820132677200_R43","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1084\/JEM.182.5.1181","article-title":"Migration of human inflammatory cells into the lung results in the remodeling of arachidonic acid into a triglyceride pool.","volume":"182","author":"Triggiani","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025102820132677200_R44","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1101\/GAD.215293.113","article-title":"Unliganded progesterone receptor-mediated targeting of an RNA-containing repressive complex silences a subset of hormone-inducible genes.","volume":"27","author":"Vicent","year":"2013","journal-title":"Genes Dev."},{"key":"2025102820132677200_R45","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1210\/ENDO-119-2-527","article-title":"Advancement of uterine secretion of prostaglandin E2 by treatment with progesterone and transfer of asynchronous embryos.","volume":"119","author":"Vincent","year":"1986","journal-title":"Endocrinology"},{"key":"2025102820132677200_R46","first-page":"141","article-title":"Cytoplasmic lipid bodies of human eosinophils: subcellular isolation and analysis of arachidonate incorporation.","volume":"138","author":"Weller","year":"1991","journal-title":"Am. J. Pathol."},{"key":"2025102820132677200_R47","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/J.1600-0897.1987.TB00116.X","article-title":"Progesterone enhancement of prostaglandin E2 production by fetal placental macrophages.","volume":"14","author":"Yagel","year":"1987","journal-title":"Am. J. Reprod. Immunol. Microbiol."},{"key":"2025102820132677200_R48","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1080\/02699050500284218","article-title":"The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.","volume":"24","author":"Yoon","year":"2006","journal-title":"Growth Factors"},{"key":"2025102820132677200_R49","first-page":"759","article-title":"Co-compartmentalization of MAP kinases and cytosolic phospholipase A2 at cytoplasmic arachidonate-rich lipid bodies.","volume":"152","author":"Yu","year":"1998","journal-title":"Am. J. Pathol."},{"key":"2025102820132677200_R50","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1073\/PNAS.0336132100","article-title":"Cloning, expression and characterisation of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes.","volume":"100","author":"Zhu","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2025102820132677200_R51","article-title":"Change of plasma progesterone level of mouse at different phases [In Chinese].","volume":"36","author":"Zhu","year":"2008","journal-title":"J. Anhui Agri. [Anhui Nongye Kexue]"}],"container-title":["Reproduction, Fertility and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/33\/3\/209\/316944\/rd20195.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/33\/3\/209\/316944\/rd20195.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:13:34Z","timestamp":1761696814000},"score":1,"resource":{"primary":{"URL":"https:\/\/connectsci.au\/rd\/article\/33\/3\/209\/50685\/Effects-of-progesterone-on-the-lipolysis-of-lipid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,2,4]]}},"URL":"https:\/\/doi.org\/10.1071\/rd20195","relation":{},"ISSN":["1031-3613","1448-5990"],"issn-type":[{"type":"print","value":"1031-3613"},{"type":"electronic","value":"1448-5990"}],"subject":[],"published":{"date-parts":[[2021,1,28]]}}}