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

Hyo Jin Park, Sun Ji Park, Deog Bon Koo, Sang Rae Lee, Il Keun Kong, Jae Woong Ryoo, Young Il Park, Kyu Tae Chang, Dong Seok Lee

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalLife Sciences
Volume113
Issue number1-2
DOIs
StatePublished - 15 Sep 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Inc.

Keywords

  • Corpus luteum
  • ER stress
  • Luteal phase
  • Progesterone production
  • Unfolded protein response

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