Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice

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Title
Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice
Author(s)
H J Park; S J Park; D B Koo; Sang-Rae Lee; I K Kong; J W Ryoo; Y I Park; Kyu Tae Chang; D S Lee
Bibliographic Citation
Life Sciences, vol. 113, no. 1, pp. 60-67
Publication Year
2014
Abstract
Aims: 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. Main 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. Key findings: 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. Significance: 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.
Keyword
Corpus luteumER stressLuteal phaseProgesterone productionUnfolded protein response
ISSN
0024-3205
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.lfs.2014.07.033
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
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