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.
Similar content being viewed by others
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.
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.
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.
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.
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.
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.
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.
Hill C. S. and Treisman R. (1995) Transcriptional regulation by extracellular signals: mechanisms and specificity.Cell 80, 199–211.
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.
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.
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.
Kovács K. J. and Mezey É. (1987) Dexamethasone inhibits corticotropin-releasing factor gene expression in the paraventricular nucleus.Neuroendocrinology 46, 365–368.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02736792