Jurek, Benjamin and Slattery, David A. and Hiraoka, Yuichi and Liu, Ying and Nishimori, Katsuhiko and Aguilera, Greti and Neumann, Inga D. and van den Burg, Erwin H. (2015) Oxytocin Regulates Stress-Induced Crf Gene Transcription through CREB-Regulated Transcription Coactivator 3. JOURNAL OF NEUROSCIENCE, 35 (35). pp. 12248-12260. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
The major regulator of the neuroendocrine stress response in the brain is corticotropin releasing factor (CRF), whose transcription is controlled by CREB and its cofactors CRTC2/3 (TORC2/3). Phosphorylated CRTCs are sequestered in the cytoplasm, but rapidly dephosphorylated and translocated into the nucleus following a stressful stimulus. As the stress response is attenuated by oxytocin (OT), we tested whether OT interferes with CRTC translocation and, thereby, Crf expression. OT(1 nmol, i.c.v.) delayed the stress-induced increase of nuclear CRTC3 and Crf hnRNA levels in the paraventricular nucleus of male rats and mice, but did not affect either parameter in the absence of the stressor. The increase in Crf hnRNA levels at later time points was parallel to elevated nuclear CRTC2/3 levels. A direct effect of Thr(4) Gly(7)-OT (TGOT) on CRTC3 translocation and Crf expression was found in rat primary hypothalamic neurons, amygdaloid (Ar-5), hypothalamic (H32), and human neuroblastoma (Be(2)M17) cell lines. CRTC3, but not CRCT2, knockdown using siRNA in Be(2)M17 cells prevented the effect of TGOT on Crf hnRNA levels. Chromatin-immunoprecipitation demonstrated that TGOT reduced CRTC3, but not CRTC2, binding to the Crf promoter after 10 min of forskolin stimulation. Together, the results indicate that OT modulates CRTC3 translocation, the binding of CRTC3 to the Crf promoter and, ultimately, transcription of the Crf gene.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RNA EXPRESSION; STRIA TERMINALIS; BRAIN OXYTOCIN; BED NUCLEUS; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; HORMONE TRANSCRIPTION; MYOMETRIAL CELLS; LACTATING RATS; Crf; CRTC3/TORC3; intracellular signaling; oxytocin receptor; stress response |
| Subjects: | 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2019 12:02 |
| Last Modified: | 07 Jun 2019 12:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4841 |
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