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Regulation of stress-induced transcriptional changes in the hypothalamic neurosecretory neurons

Journal of Molecular Neuroscience volume 7, pages 125–133 (1996)Cite this article

Abstract

Transcriptional changes in corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) gene expression were studied byin situ hybridization histochemistry using cRNA probes directed against intronic sequences. Acute ether stress resulted in a rapid induction of CRF and a delayed activation of vasopressin heteronuclear (hn)RNA in the parvocellular neurosecretory neurons within the paraventricular nucleus (PVN) of the hypothalamus. To explore possible molecular mechanisms regulating stress-related neuropeptide expression in vivo, the time-courses of stress-induced activation of different transcription factor classes were compared to that of changes in neuropeptide transcription. The peak of CRF transcription was parallel to that of cAMP response-element binding protein (CREB) phosphorylation but preceded the induction of c-fos and NGFI-B mRNAs and Fos protein. In contrast, AVP expression occurred in step with immediate-early gene (IEG) responses, suggesting involvement of different mechanisms underlying stress-induced neuropeptide responses. The interference of glucocorticoid hormones with stress-induced neuropeptide and transcription-factor responses has also been revealed in rats acutely or chronically pretreated with glucocorticoids. Acute dexamethasone injection did not prevent neuropeptide and transcription factor responses to ether inhalation, whereas chronic corticosterone administration completely blocked IEG and neuropeptide induction in the stress-related neurosecretory neurons.

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References

  • Antoni F. A. (1986) Hypothalamic control of adrenocorticotropin secretion: advances since the discovery of 41-residue corticotropin-releasing factor.Endocrine Rev. 7, 351–378.

    CAS  Article  Google Scholar 

  • Ceccatelli S., Villar M. J., Goldstein M., and Hökfelt T. (1989) Expression of c-fos immunoreactivity in transmitter-characterized neurons after stress.Proc. Natl. Acad. Sci. USA 86, 9569–9573.

    PubMed  Article  CAS  Google Scholar 

  • Chan R. K. W., Brown E. R., Ericsson A., Kovács K. J., and Sawchenko P. E. (1993) A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry.J. Neurosci. 13, 5126–5138.

    PubMed  CAS  Google Scholar 

  • Dallman M. F., Akana S. F., Cascio C. S., Darlington D. N., Jacobson L., and Levin N. (1987) Regulation of ACTH secretion: variations on a theme of B.Recent Progr. Hormone Res. 43, 113–173.

    PubMed  CAS  Google Scholar 

  • Drouin J., Trifiro M. A., Plante R. K., Nemer M., Eriksson P., and Wrange Ö. (1989) Glucocorticoid receptor binding to a specific DNA sequence required for hormone-dependent inhibition of pro-opiomelanocortin gene transcription.Mol. Cell Biol. 9, 5305.

    PubMed  CAS  Google Scholar 

  • Gonzalez G. A. and Montminy M. R. (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.Cell 59, 675–680.

    PubMed  Article  CAS  Google Scholar 

  • Hagiwara M., Brindle P., Harootunian A., Armstrong R., Rivier J., Vale W., Tsien R., and Montminy M. R. (1993) Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A.Mol. Cell Biol. 13, 4852–4859.

    PubMed  CAS  Google Scholar 

  • Hill C. S. and Treisman R. (1995) Transcriptional regulation by extracellular signals: mechanisms and specificity.Cell 80, 199–211.

    PubMed  Article  CAS  Google Scholar 

  • Herman J. P., Schafer M. K.-H., Watson S. J., and Sherman T. G. (1991) In situ hybridization analysis of arginine vasopressin gene transcription using intron-specific probes.Mol. Endocrinol. 5, 1447–1456.

    PubMed  CAS  Google Scholar 

  • Herman J. P., Schafer M., Thompson R. C., and Watson S. J. (1992) Rapid regulation of corticotropin-releasing gene transcription in vivo.Mol. Endocrinol. 6, 1061–1069.

    PubMed  Article  CAS  Google Scholar 

  • Kiss J. Z., Mezcy E., and Skirboll L. (1984) Corticotropin-releasing factor—immunoreactive neurons of the paraventricular nucleus become vasopressin positive after adrenalectomy.Proc. Natl. Acad. Sci. USA 81, 1854–1858.

    PubMed  Article  CAS  Google Scholar 

  • Kovács K. J. and Mezey É. (1987) Dexamethasone inhibits corticotropin-releasing factor gene expression in the paraventricular nucleus.Neuroendocrinology 46, 365–368.

    PubMed  Google Scholar 

  • Kovács K. J. and Makara G. B. (1990) Partial deafferentation of the hypothalamic paraventricular nucleus: effect on the stress- or adrenalectomy-induced ACTH secretion.Neuroendocrinol. Lett. 12, 383–389.

    Google Scholar 

  • Kovács K. J. and Sawchenko P. E. (1996) Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons.J. Neurosci. 16, 262–273.

    PubMed  Google Scholar 

  • Lightman S. L. and Young W. S. III (1988) Corticotropin-releasing factor, vasopressin and proopiomelanocortin mRNA responses to stress and opiates in the rat.J. Physiol. 403, 511–523.

    PubMed  CAS  Google Scholar 

  • Sassone-Corsi P., Visvader J., Ferland L., Mellon P. L., and Verma I. M. (1988) Induction of proto-oncogene fos transcription through the adenylate-cyclase pathway: characterization of c-AMP-responsive element.Genes Dev. 2, 1529–1538.

    PubMed  Article  CAS  Google Scholar 

  • Sawchenko P. E. and Swanson L. W. (1983) The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat.J. Comp. Neurol. 218, 121–144.

    PubMed  Article  CAS  Google Scholar 

  • Sawchenko P. E., Swanson L. W., and Vale W. W. (1984) Co-expression of corticotropin-releasing factor and vasopressin immunoreactivity in parvocellular neurosecretory neurons of the adrenalectomized rat.Proc. Natl. Acad. Sci. USA 81, 1883–1887.

    PubMed  Article  CAS  Google Scholar 

  • Sawchenko P. E., Imaki T., Potter E., Kovács K. J., and Vale W. (1993) The functional neuroanatomy of corticotropin-releasing factor, inCorticotropin-Releasing Factor, Ciba Foundation Symposium 172 (Chadwick D. J., Marsh J., and Ackrill K., eds.), Wiley, Chichester, pp. 5–29.

    Chapter  Google Scholar 

  • Schule R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., and Evans R. M. (1990) Functional antagonism between oncoprotein c-jun and the glucocorticoid receptor.Cell 62, 1217–1226.

    PubMed  Article  CAS  Google Scholar 

  • Seasholtz A. F., Thompson R. C., and Douglass J. O. (1988) Identification of a cyclic adenosine monophosphate-responsive element in the rat corticotropin-releasing hormone gene.Mol. Endocrinol. 2, 1311–1319.

    PubMed  CAS  Google Scholar 

  • Sheng M. and Greenberg M. E. (1990) The regulation and function of c-fos and other immediate early genes in the nervous system.Neuron 4, 477–485.

    PubMed  Article  CAS  Google Scholar 

  • Swanson L. W. and Simmonds D. M. (1989) Differential steroid hormone and neural influences on peptide mRNA levels in CRH cells of the paraventricular nucleus: a hybridization histochemical study in the rat.J. Comp. Neurol. 285, 413–435.

    PubMed  Article  CAS  Google Scholar 

  • Uht R. M., McKelvy J. F., Harrison R. W., and Bohn M. C. (1988) Demonstration of glucocorticoid receptor-like immunoreactivity in glucocorticoid-sensitive vasopressin and corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus.J. Neurosci. Res. 19, 405–411.

    PubMed  Article  CAS  Google Scholar 

  • Vale W., Speiss J., Rivier C., and Rivier J. (1983) Characterization of a 41-residue ovine hypothalamic peptide that stimulates the secretions of corticotropin and β-endorphin.Science 213, 1394–1397.

    Article  Google Scholar 

  • Verbeeck M. A. E., Adan R. A. H., and Burbach J. P. H. (1990) Vasopressin gene expression is stimulated by cyclic AMP in homologous and heterologous expression systems.FEBS Lett. 272, 89–93.

    PubMed  Article  CAS  Google Scholar 

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Affiliations

  1. Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary

    Krisztina J. Kovács & Paul E. Sawchenko

  2. Laboratory of Neuronal Structure and Function, The Salk Institute, La Jolla, CA

    Krisztina J. Kovács & Paul E. Sawchenko

Authors
  1. Krisztina J. Kovács
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  2. Paul E. Sawchenko
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Kovács, K.J., Sawchenko, P.E. Regulation of stress-induced transcriptional changes in the hypothalamic neurosecretory neurons. J Mol Neurosci 7, 125–133 (1996). https://doi.org/10.1007/BF02736792

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  • DOI: https://doi.org/10.1007/BF02736792

Index Entries

  • Stress
  • corticotropin-releasing factor
  • vasopressin
  • CREB
  • transcription factors