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Specific and time-dependent effects of glucocorticoid receptor agonist RU28362 on stress-induced pro-opiomelanocortin hnRNA, c-fos mRNA and zif268 mRNA in the pituitary.
J Neuroendocrinol 2006; 18(2):129-38JN

Abstract

This study examined the effects of the glucocorticoid receptor (GR) agonist RU28362 on stress-induced gene expression in the pituitary of rats to investigate mechanisms of glucocorticoid negative feedback in vivo. In an initial experiment, acute restraint stress produced rapid (within 15 min) induction of c-fos mRNA, zif268 mRNA and pro-opiomelanocortin (POMC) hnRNA within the anterior and intermediate/posterior pituitary as determined by quantitative real-time polymerase chain reaction. Treatment with RU28362 (150 microg/kg, i.p.) 60 min before restraint inhibited adrenocorticotrophic hormone (ACTH) and corticosterone secretion and selectively suppressed the stress-induced increase in POMC hnRNA in the anterior pituitary gland. The failure of RU28362 to surpress the stress-induced rise in c-fos and expression of zif268 mRNA suggests that the central release of ACTH secretagogues was not affected at this time point by treatment with the GR agonist. Rather, the inhibition of ACTH release appeared to be due to a direct effect of RU28362 within the pituitary. A follow-up time-course study varied the interval (10, 60 or 180 min) between RU28362 pretreatment and the onset of restraint. The stress-induced increase in POMC hnRNA was completely blunted by RU28362 treatment within 10 min of treatment, although the stress induced hormone secretion, c-fos mRNA and zif268 mRNA were unaffected. The rapid inhibition of the stress-induced rise in POMC hnRNA in the anterior pituitary appears to reflect direct, GR-mediated suppression of POMC gene expression. RU28362 pretreatment 180 min before restraint onset was sufficient to suppress the stress-induced expression in the anterior pituitary gland of all three genes examined. Thus, the delayed negative feedback effects on hypothalamic-pituitary-adrenal axis activity that emerged after 180 min after glucocorticoid treatment were not evident at 60 min. Taken together, the data suggest that the inhibition of the stress-induced release of ACTH apparent within the first hour of glucocorticoid exposure is effected at the level of the pituitary gland. The delayed glucocorticoid effects evident 180 min after RU28362 treatment may include glucocorticoid actions in the brain and additional actions within the pituitary.

Authors+Show Affiliations

Department of Psychology and Center for Neurosciences, University of Colorado at Boulder, USA. aginsber@itsa.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16420282

Citation

Ginsberg, A B., et al. "Specific and Time-dependent Effects of Glucocorticoid Receptor Agonist RU28362 On Stress-induced Pro-opiomelanocortin hnRNA, C-fos mRNA and Zif268 mRNA in the Pituitary." Journal of Neuroendocrinology, vol. 18, no. 2, 2006, pp. 129-38.
Ginsberg AB, Frank MG, Francis AB, et al. Specific and time-dependent effects of glucocorticoid receptor agonist RU28362 on stress-induced pro-opiomelanocortin hnRNA, c-fos mRNA and zif268 mRNA in the pituitary. J Neuroendocrinol. 2006;18(2):129-38.
Ginsberg, A. B., Frank, M. G., Francis, A. B., Rubin, B. A., O'Connor, K. A., & Spencer, R. L. (2006). Specific and time-dependent effects of glucocorticoid receptor agonist RU28362 on stress-induced pro-opiomelanocortin hnRNA, c-fos mRNA and zif268 mRNA in the pituitary. Journal of Neuroendocrinology, 18(2), pp. 129-38.
Ginsberg AB, et al. Specific and Time-dependent Effects of Glucocorticoid Receptor Agonist RU28362 On Stress-induced Pro-opiomelanocortin hnRNA, C-fos mRNA and Zif268 mRNA in the Pituitary. J Neuroendocrinol. 2006;18(2):129-38. PubMed PMID: 16420282.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific and time-dependent effects of glucocorticoid receptor agonist RU28362 on stress-induced pro-opiomelanocortin hnRNA, c-fos mRNA and zif268 mRNA in the pituitary. AU - Ginsberg,A B, AU - Frank,M G, AU - Francis,A B, AU - Rubin,B A, AU - O'Connor,K A, AU - Spencer,R L, PY - 2006/1/20/pubmed PY - 2006/4/28/medline PY - 2006/1/20/entrez SP - 129 EP - 38 JF - Journal of neuroendocrinology JO - J. Neuroendocrinol. VL - 18 IS - 2 N2 - This study examined the effects of the glucocorticoid receptor (GR) agonist RU28362 on stress-induced gene expression in the pituitary of rats to investigate mechanisms of glucocorticoid negative feedback in vivo. In an initial experiment, acute restraint stress produced rapid (within 15 min) induction of c-fos mRNA, zif268 mRNA and pro-opiomelanocortin (POMC) hnRNA within the anterior and intermediate/posterior pituitary as determined by quantitative real-time polymerase chain reaction. Treatment with RU28362 (150 microg/kg, i.p.) 60 min before restraint inhibited adrenocorticotrophic hormone (ACTH) and corticosterone secretion and selectively suppressed the stress-induced increase in POMC hnRNA in the anterior pituitary gland. The failure of RU28362 to surpress the stress-induced rise in c-fos and expression of zif268 mRNA suggests that the central release of ACTH secretagogues was not affected at this time point by treatment with the GR agonist. Rather, the inhibition of ACTH release appeared to be due to a direct effect of RU28362 within the pituitary. A follow-up time-course study varied the interval (10, 60 or 180 min) between RU28362 pretreatment and the onset of restraint. The stress-induced increase in POMC hnRNA was completely blunted by RU28362 treatment within 10 min of treatment, although the stress induced hormone secretion, c-fos mRNA and zif268 mRNA were unaffected. The rapid inhibition of the stress-induced rise in POMC hnRNA in the anterior pituitary appears to reflect direct, GR-mediated suppression of POMC gene expression. RU28362 pretreatment 180 min before restraint onset was sufficient to suppress the stress-induced expression in the anterior pituitary gland of all three genes examined. Thus, the delayed negative feedback effects on hypothalamic-pituitary-adrenal axis activity that emerged after 180 min after glucocorticoid treatment were not evident at 60 min. Taken together, the data suggest that the inhibition of the stress-induced release of ACTH apparent within the first hour of glucocorticoid exposure is effected at the level of the pituitary gland. The delayed glucocorticoid effects evident 180 min after RU28362 treatment may include glucocorticoid actions in the brain and additional actions within the pituitary. SN - 0953-8194 UR - https://www.unboundmedicine.com/medline/citation/16420282/Specific_and_time_dependent_effects_of_glucocorticoid_receptor_agonist_RU28362_on_stress_induced_pro_opiomelanocortin_hnRNA_c_fos_mRNA_and_zif268_mRNA_in_the_pituitary_ L2 - https://doi.org/10.1111/j.1365-2826.2005.01396.x DB - PRIME DP - Unbound Medicine ER -