title: Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.
abstract: OBJECTIVE
  We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle.
  
  
  METHODS
  The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection.
  
  
  RESULTS
  Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased.
  
  
  CONCLUSIONS
  These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span.
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea; Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea; Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sun-Ji
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Daegu University, Gyeongbuk 712-749, Republic of Korea.
authors.forename: Deog-Bon
authors.initials: DB
authors.lastname: Koo
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Animal Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Il-Keun
authors.initials: IK
authors.lastname: Kong
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea; Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Ryoo
authors.affiliation: Graduate School Department of Digital Media, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Park
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea. Electronic address: changkt@kribb.re.kr.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
authors.affiliation: School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea; Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: lee1@knu.ac.kr.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D003338:Corpus Luteum / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004971:Estrus; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism; D008183:Luteal Phase; D051379:Mice; D008810:Mice, Inbred C57BL; D011374:Progesterone / Q000096:biosynthesis*; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D051702:Activating Transcription Factor 6; C081452:Atf4 protein, mouse; C497112:Atf6 protein, mouse; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D051701:Activating Transcription Factor 4; D011374:Progesterone
keywords: Corpus luteum; ER stress; Luteal phase; Progesterone production; Unfolded protein response