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Progesterone, but not estradiol, synchronizes circadian oscillator in the uterus endometrial stromal cells

Molecular and Cellular Biochemistry volume 324, Article number: 31 (2009) Cite this article

Abstract

The circadian oscillator is generated within the suprachiasmatic nuclei and synchronizes circadian clocks in numerous peripheral tissues. The molecular basis is composed of a number of genes and proteins that form transcriptional and translational feedback loops. Such molecular oscillators are also operative in peripheral tissues, including in the uterus. Although ovarian steroids regulate the function of uterine endometrial stromal cells, the modulation of ovarian steroids on the circadian rhythms remains unknown. Here we investigate the possibility that estradiol (E2) and progesterone (P4) modulate the circadian oscillator of the stromal cells. The study using transgenic rats constructed with Period 2 (Per2) promoter-destabilized luciferase (Per2-dLuc) gene, with the real-time monitoring system of Per2-dLuc oscillation. The stromal cells displayed constant Per2-dLuc oscillation after treatment with dexamethasone, suggesting that the circadian oscillator is operative. However, the circadian oscillator was disrupted by in vivo administration of human chorionic gonadotropin (hCG) following equine chorionic gonadotropin (eCG), although it was altered into a rhythmic pattern 4 days later following hCG. Chronic treatment with P4 induced constant Per2-dLuc oscillation in the stromal cells from eCG-treated immature and pregnant rats, whereas E2 did not promote such a rhythmic Per2-dLuc oscillation. Collectively, P4 synchronizes the circadian oscillator of the uterus endometrial stromal cells through transcriptional and translational feedback loops of the clockwork system.

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Acknowledgments

We are grateful to Christopher Wood (Zhejiang University) for his critical reading of the manuscript. This research was supported in part by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Sciences (JSPS; 16380200) (to M-A H).

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Affiliations

  1. Laboratory of Reproductive Physiology and Biotechnology, Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Fukuoka-shi, Fukuoka, 812-8581, Japan

    Masami Hirata, Pei-Jian He, Nozomi Shibuya, Miho Uchikawa, Nobuhiko Yamauchi & Masa-aki Hattori

  2. Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc, Miyukigaoka 21, Tsukuba-shi, Ibaraki, 305-8585, Japan

    Seiichi Hashimoto

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  1. Masami Hirata
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  2. Pei-Jian He
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  3. Nozomi Shibuya
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  4. Miho Uchikawa
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  5. Nobuhiko Yamauchi
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  7. Masa-aki Hattori
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Correspondence to Masa-aki Hattori.

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Hirata, M., He, PJ., Shibuya, N. et al. Progesterone, but not estradiol, synchronizes circadian oscillator in the uterus endometrial stromal cells. Mol Cell Biochem 324, 31 (2009). https://doi.org/10.1007/s11010-008-9981-4

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  • DOI: https://doi.org/10.1007/s11010-008-9981-4

Keywords

  • Circadian clockwork
  • Per2-dLuc oscillation
  • Uterus endometrial stromal cells
  • Progesterone
  • Estradiol