Skip to main content

Gonadotropic regulation of circadian clockwork in rat granulosa cells

Molecular and Cellular Biochemistry volume 302, pages 111–118 (2007)Cite this article

Abstract

The circadian clock is responsible for the generation of circadian rhythms in hormonal secretion and metabolism. These peripheral clocks could be reset by various cues in order to adapt to environmental variations. The ovary can be characterized as having highly dynamic physiology regulated by gonadotropins. Here, we aimed to address the status of circadian clock in the ovary, and to explore how gonadotropins could regulate clockwork in granulosa cells (GCs). To this end, we mainly utilized the immunohistochemistry, RT-PCR, and real-time monitoring of gene expression methods. PER1 protein was constantly abundant across the daily cycle in the GCs of immature ovaries. In contrast, PER1 protein level was obviously cyclic through the circadian cycle in the luteal cells of pubertal ovaries. In addition, both FSH and LH induced Per1 expression in cultured immature and mature GCs, respectively. The promoter analysis revealed that the Per1 expression was mediated by the cAMP response element binding protein. In cultured transgenic GCs, both FSH and LH also induced the circadian oscillation of Per2. However, the Per2 oscillation promoted by FSH quickly dampened within only one cycle, whereas the Per2 oscillation promoted by LH was persistently maintained. Collectively, these findings strongly suggest that both FSH and LH play an important role in regulating circadian clock in the ovary; however, they might exert differential actions on the clockwork in vivo due to each specific role within ovarian physiology.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Reference

  1. Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96:271–290

    PubMed  Article  CAS  Google Scholar 

  2. Reppert SM, Weaver DR (2001) Molecular analysis of mammalian circadian rhythms. Annu Rev Physiol 63:647–676

    PubMed  Article  CAS  Google Scholar 

  3. Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ (1998) Role of the CLOCK protein in the mammalian circadian mechanism. Science 280:1564–1569

    PubMed  Article  CAS  Google Scholar 

  4. Shearman LP, Sriram S, Weaver DR, Maywood ES, Chaves I, Zheng B, Kume K, Lee CC, van der Horst GT, Hastings MH, Reppert SM (2000) Interacting molecular loops in the mammalian circadian clock. Science 288:1013–1019

    PubMed  Article  CAS  Google Scholar 

  5. Ueda HR, Hayashi S, Chen W, Sano M, Machida M, Shigeyoshi Y, Iino M, Hashimoto S (2005) System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nat Genet 37:187–192

    PubMed  Article  CAS  Google Scholar 

  6. Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T, Takumi T (2004) Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. BMC Mol Biol 5:18

    PubMed  Article  CAS  Google Scholar 

  7. Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14:2950–2961

    PubMed  Article  CAS  Google Scholar 

  8. Schibler U, Sassone-Corsi P (2002) A web of circadian pacemakers. Cell 111:919–922

    PubMed  Article  CAS  Google Scholar 

  9. Balsalobre A, Brown SA, Marcacci L, Tronche F, Kellendonk C, Reichardt HM, Schutz G, Schibler U (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289:2344–2347

    PubMed  Article  CAS  Google Scholar 

  10. Balsalobre A, Marcacci L, Schibler U (2000) Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts. Curr Biol 10:1291–1294

    PubMed  Article  CAS  Google Scholar 

  11. Nakamura TJ, Moriya T, Inoue S, Shimazoe T, Watanabe S, Ebihara S, Shinohara K (2005) Estrogen differentially regulates expression of Per1 and Per2 genes between central and peripheral clocks and between reproductive and nonreproductive tissues in female rats. J Neurosci Res 82:622–630

    PubMed  Article  CAS  Google Scholar 

  12. Tsuchiya Y, Minami I, Kadotani H, Nishida E (2005) Resetting of peripheral circadian clock by prostaglandin E2. EMBO Rep 6:256–261

    PubMed  Article  CAS  Google Scholar 

  13. Hinoi E, Ueshima T, Hojo H, Iemata M, Takarada T, Yoneda Y (2006) Up-regulation of per mRNA expression by parathyroid hormone through a protein kinase A-CREB-dependent mechanism in chondrocytes. J Biol Chem 281:23632–23642

    PubMed  Article  CAS  Google Scholar 

  14. Fahrenkrug J, Georg B, Hannibal J, Hindersson P, Gras S (2006) Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary. Endocrinology 147:3769–3776

    PubMed  Article  CAS  Google Scholar 

  15. Karman BN, Tischkau SA (2006) Circadian clock gene expression in the ovary: effects of luteinizing hormone. Biol Reprod 75:624–632

    PubMed  Article  CAS  Google Scholar 

  16. McGee EA, Hsueh AJ (2000) Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21:200–214

    PubMed  Article  CAS  Google Scholar 

  17. Richards JS (1994) Hormonal control of gene expression in the ovary. Endocr Rev 15:725–751

    PubMed  Article  CAS  Google Scholar 

  18. Mukherjee A, Park-Sarge OK, Mayo KE (1996) Gonadotropins induce rapid phosphorylation of the 3′, 5′-cyclic adenosine monophosphate response element binding protein in ovarian granulosa cells. Endocrinology 137:3234–3245

    PubMed  Article  CAS  Google Scholar 

  19. Tischkau SA, Mitchell JW, Tyan SH, Buchanan GF, Gillette MU (2002) Ca2+/cAMP response element-binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock. J Biol Chem 278:718–723

    PubMed  Article  Google Scholar 

  20. Yagita K, Okamura H (2000) Forskolin induces circadian gene expression of rper1, rper2 and dbp in mammalian rat-1 fibroblasts. FEBS Lett 465:79–82

    PubMed  Article  CAS  Google Scholar 

  21. Travnickova-Bendova Z, Cermakian N, Reppert SM, Sassone-Corsi P (2002) Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc Natl Acad Sci USA 99:7728–7733

    PubMed  Article  CAS  Google Scholar 

  22. Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S, Iino M, Shigeyoshi Y, Hashimoto S (2002) A transcription factor response element for gene expression during circadian night. Nature 418:534–539

    PubMed  Article  CAS  Google Scholar 

  23. He PJ, Fujimoto Y, Yamauchi N, Hattori M-A (2006) Real-time monitoring of cAMP response element binding protein signaling in porcine granulosa cells modulated by ovarian factors. Mol Cell Biochem 290:177–184

    PubMed  Article  CAS  Google Scholar 

  24. Hattori M-A, Sakamoto K, Fujihara N, Kojima I (1996) Nitric oxide: a modulator for the epidermal growth factor receptor expression in developing granulosa cells. Am J Physiol Cell Physiol 270:C812–C818

    CAS  Google Scholar 

  25. Shigeyoshi Y, Taguchi K, Yamamoto S, Takekida S, Yan L, Tei H, Moriya T, Shibata S, Loros JJ, Dunlap JC, Okamura H (1997) Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript. Cell 91:1043–1053

    PubMed  Article  CAS  Google Scholar 

  26. Alvarez JD, Sehgal A (2005) The thymus is similar to the testis in its pattern of circadian clock gene expression. J Biol Rhythms 20:111–121

    PubMed  Article  CAS  Google Scholar 

  27. Alvarez JD, Chen D, Storer E, Sehgal A (2003) Non-cyclic and developmental stage-specific expression of circadian clock proteins during murine spermatogenesis. Biol Reprod 69:81–91

    PubMed  Article  CAS  Google Scholar 

  28. Beaver LM, Rush BL, Gvakharia BO, Giebultowicz JM (2003) Noncircadian regulation and function of clock genes period and timeless in oogenesis of Drosophila melanogaster. J Biol Rhythms 18:463–472

    PubMed  Article  CAS  Google Scholar 

  29. Balsalobre A, Damiola F, Schibler U (1998) A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93:929–937

    PubMed  Article  CAS  Google Scholar 

  30. Conti M (2002) Specificity of the cyclic adenosine 3′,5′-monophosphate signal in granulosa cell function. Biol Reprod 67:1653–1661

    PubMed  Article  CAS  Google Scholar 

  31. Yazawa T, Mizutani T, Yamada K, Kawata H, Sekiguchi T, Yoshino M, Kajitani T, Shou Z, Miyamoto K (2003) Involvement of cyclic adenosine 5′-monophosphate response element-binding protein, steroidogenic factor 1, and Dax-1 in the regulation of gonadotropin-inducible ovarian transcription factor 1 gene expression by follicle-stimulating hormone in ovarian granulosa cells. Endocrinology 144:1920–1930

    PubMed  Article  CAS  Google Scholar 

  32. Pei L, Dodson R, Schoderbek WE, Maurer RA, Mayo KE (1991) Regulation of the alpha inhibin gene by cyclic adenosine 3′, 5′-monophosphate after transfection into rat granulosa cells. Mol Endocrinol 5:521–534

    PubMed  CAS  Article  Google Scholar 

  33. Carlone DL, Richards JS (1997) Evidence that functional interactions of CREB and SF-1 mediate hormone regulated expression of the aromatase gene in granulosa cells and constitutive expression in R2C cells. J Steroid Biochem Mol Biol 61:223–231

    PubMed  CAS  Google Scholar 

  34. Clem BF, Hudson EA, Clark BJ (2005) Cyclic adenosine 3′,5′-monophophate (cAMP) enhances cAMP-responsive binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter. Endocrinology 146:1348–1356

    PubMed  Article  CAS  Google Scholar 

  35. Morse D, Cermakian N, Brancorsini S, Parvinen M, Sassone-Corsi P (2003) No circadian rhythms in testis: Period1 expression is clock independent and developmentally regulated in the mouse. Mol Endocrinol 17:141–151

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgements

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).

Author information

Affiliations

  1. Laboratory of Reproductive Physiology and Biotechnology, Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Pei-Jian He, Masami Hirata, 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

Authors
  1. Pei-Jian He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masami Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nobuhiko Yamauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seiichi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masa-aki Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masa-aki Hattori.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

He, PJ., Hirata, M., Yamauchi, N. et al. Gonadotropic regulation of circadian clockwork in rat granulosa cells. Mol Cell Biochem 302, 111–118 (2007). https://doi.org/10.1007/s11010-007-9432-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9432-7

Keywords

  • Gonadotropins
  • Circadian clock
  • Transgenic rat
  • Per1
  • CREB