Light Regulates c-fos Gene Expression in the Hamster SCN: Implications for Circadian and Seasonal Control of Reproduction

  • Jon M. Kornhauser
  • Dwight E. Nelson
  • Kelly E. Mayo
  • Joseph S. Takahashi
Part of the Serono Symposia USA book series (SERONOSYMP)


The naturally occurring daily cycle of light and darkness in the environment exerts important control upon the function of the reproductive system in mammals, providing external timing cues that influence reproductive physiology in two distinct ways. First, the light-dark cycle serves to synchronize the circadian timekeeping system, and this circadian pacemaker regulates daily periodic events of the neuroendocrine axis. Second, many mammals breed on a seasonal basis, and the length of the day is the most important environmental factor regulating these dramatic seasonal changes in reproduction. The circadian pacemaking system mediates effects of this type by measuring changes in the photoperiod corresponding to seasonal alterations in day length (1). The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the predominant circadian pacemaker regulating behavioral and physiological processes in mammals, including the reproductive axis, (2–4). Timing signals from this pacemaker coordinate circadian components of reproductive rhythms; for example, the time of occurrence of the preovulatory surges in luteinizing hormone (LH) and follicle stimulating hormone (FSH) and of ovulation during proestrus (1, 5). The SCN also mediates the effects of alterations in photoperiod on seasonal changes in reproductive function. Thus, the circadian pacemaker in the SCN utilizes photic information for synchronization of endogenous rhythms to the environmental 24-h light cycle and for measurement of changes in day length for photoperiodic regulation of reproduction.


Nerve Growth Factor Circadian Rhythm Circadian Clock Golden Hamster Suprachiasmatic Nucleus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Turek FW, Van Cauter E. Rhythms in reproduction. In: Knobil E, Neill J, et al., eds. The physiology of reproduction. New York: Raven Press, 1988; 1789–830.Google Scholar
  2. 2.
    Moore RY. Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc 1983; 42: 2783–9.PubMedGoogle Scholar
  3. 3.
    Rusak B, Zucker I. Neural regulation of circadian rhythms. Physiol Rev 1979; 59: 449–526.PubMedGoogle Scholar
  4. 4.
    Meijer JH, Rietveld WJ. Neurophysiology of the suprachiasmatic circadian pacemaker in rodents. Physiol Rev 1989; 69: 671–707.PubMedGoogle Scholar
  5. 5.
    Stetson MH, Anderson PJ. Circadian pacemaker times gonadotropin release in free-running female hamsters. Am J Physiol 1980; 238: R23–7.PubMedGoogle Scholar
  6. 6.
    Nelson DE, Takahashi JS. Sensitivity of the visual pathway for entrainment of a circadian pacemaker: temporal integration of photic inputs. J Physiol (Lond) (in press).Google Scholar
  7. 7.
    Müller R, Bravo R, Burckhardt J, Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 1984; 312: 716–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Greenberg ME, Ziff EB. Stimulation of 3T3 cells induces transcription of the c-fos protooncogene. Nature 1984; 311: 433–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Lau LF, Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci USA 1987; 84: 1182–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Sassone-Corsi P, Lamph WW, Verma IM. Regulation of proto-oncogene fos: a paradigm for early response genes. Cold Spring Harbor Symp Quant Biol 1988; 53: 749–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Curran T, Franza BR. Fos and Jun: the AP-1 connection. Cell 1988; 55: 395–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Goelet P, Castellucci VF, Schacher S, Kandel ER. The long and short of longterm memory—a molecular framework. Nature 1986; 322: 419–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Cole AJ, Saffen DW, Baraban JM, Worley PF. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 1989; 340: 474–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science 1989; 245: 371–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Van Beveren C, van Straaten F, Curran T, Müller R, Verma IM. Analysis of FBJMuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Cell 1983; 32: 1241–55.PubMedCrossRefGoogle Scholar
  16. 16.
    Rauscher FJ III, Cohen DR, Curran T, et al. Fos-associated protein p39 is the product of the jun proto-oncogene. Science 1988; 240: 1010–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Curran T, Rauscher FJ, Cohen DR, Franza BR. Beyond the second messenger: oncogenes and transcription factors. Cold Spring Harbor Symp Quant Biol 1988; 53: 769–77.PubMedCrossRefGoogle Scholar
  18. 18.
    Kruijer W, Schubert D, Verma IM. Induction of the proto-oncogene fos by nerve growth factor. Proc Natl Acad Sci USA 1985; 82: 7330–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Milbrandt J. Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells. Proc Natl Acad Sci USA 1986; 83: 4789–93.PubMedCrossRefGoogle Scholar
  20. 20.
    Greenberg M, Ziff EB, Greene LA. Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 1986; 234: 80–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Greenberg ME, Greene LA, Ziff EB. Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells. J Biol Chem 1985; 260: 14101–10.PubMedGoogle Scholar
  22. 22.
    Morgan JI, Cohen DR, Hempstead JL, Curran T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science 1987; 237: 192–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Sagar SM, Sharp FR, Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science 1988; 240: 1328–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 1987; 328: 632–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Komhauser JM, Nelson DE, Mayo KE, Takahashi JS. Photic and circadian regulation of c-fos gene expression in the hamster suprachiasmatic nucleus. Neuron 1990; 5: 127–34.CrossRefGoogle Scholar
  26. 26.
    Rusak B, Robertson HA, Wisden W, Hunt SP. Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus. Science 1990; 248: 1237–40.PubMedCrossRefGoogle Scholar
  27. 27.
    Rea M. Light increases Fos-related protein immunoreactivity in the rat suprachiasmatic nuclei. Brain Res Bull 1989; 23: 577–81.PubMedCrossRefGoogle Scholar
  28. 28.
    Aronin N, Sagar SM, Sharp FR, Schwartz WJ. Light regulates expression of a Fos-related protein in rat suprachiasmatic nuclei. Proc Natl Acad Sci USA 1990; 87: 5959–62.PubMedCrossRefGoogle Scholar
  29. 29.
    Earnest DJ, Iadarola M, Yeh HH, Olschowka JA. Photic regulation of c-fos expression in neural components governing the entrainment of circadian rhythms. Exp neurol 1990; 109: 353–61.PubMedCrossRefGoogle Scholar
  30. 30.
    Johnson RF, Morin LP, Moore RY. Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin. Brain Res 1988; 462: 301–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Müller R, Slamon DJ, Tremblay JM, Cline MJ, Verma IM. Differential expression of cellular oncogenes during pre-and postnatal development of the mouse. Nature 1982; 299: 640–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Takahashi JS, DeCoursey PJ, Bauman L, Menaker M. Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature 1984; 308: 186–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Takahashi JS, Turek FW. Anisomycin, an inhibitor of protein synthesis, perturbs the phase of a mammalian circadian pacemaker. Brain Res 1987; 405: 199–203.PubMedCrossRefGoogle Scholar
  34. 34.
    Inouye ST, Takahashi JS, Wollnik F, Turek FW. Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN. Am J Physiol 1988; 255: R1055–8.PubMedGoogle Scholar
  35. 35.
    Wollnik F, Turek FW, Majewski P, Takahashi JS. Phase shifting the circadian clock with cycloheximide: response of hamsters with an intact or a split rhythm of locomotor activity. Brain Res 1989; 496: 82–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Pardee AB. G1 events and regulation of cell proliferation. Science 1989; 246: 603–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Montarolo PG, Goelet P, Castellucci VF, Morgan J, Kandel ER, Schacher S. A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia. Science 1986; 234: 1249–54.PubMedCrossRefGoogle Scholar
  38. 38.
    Davis HP, Squire LR. Protein synthesis and memory: a review. Psychol Bull 1984; 96: 518–59.PubMedCrossRefGoogle Scholar
  39. 39.
    Rosbash M, Hall JC. The molecular biology of circadian rhythms. Neuron 1989; 3: 387–98.PubMedCrossRefGoogle Scholar
  40. 40.
    Dunlap JC. Closely watched clocks: molecular analysis of circadian rhythms in Neurospora and Drosophila. Trends Genet 1990; 6: 159–65.PubMedCrossRefGoogle Scholar
  41. 41.
    Konopka RJ. Genetics of biological rhythms in Drosophila. Annu Rev Genet 1987; 21: 227–36.PubMedCrossRefGoogle Scholar
  42. 42.
    Young MW, Bargiello TA, Baylies MK, Saez L, Spray DC. Molecular biology of the Drosophila clock. In: Jacklet JW, ed. Neuronal and cellular oscillators. New York: Marcel Dekker, 1989: 529–42.Google Scholar
  43. 43.
    Ralph MR, Menaker M. A mutation of the circadian system in golden hamsters. Science 1988; 241: 1225–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Jon M. Kornhauser
  • Dwight E. Nelson
  • Kelly E. Mayo
  • Joseph S. Takahashi

There are no affiliations available

Personalised recommendations