Hormonal Regulation of Hypothalamic Corticotropin Releasing Hormone.
Abstract
Corticotropin Releasing Hormone (CRF) is a neuropeptide, synthesized primarily by the paraventricular nucleus of the hypothalamus in the mammalian brain. CRF plays a central role in regulating the hypothalamic-pituitary-adrenal axis, both in the maintenance of homeostasis, and in the response to stress. The expression of CRF may be regulated at several levels, including gene transcription, mRNA stability, and translational and post-translational peptide processing and secretion. Four independent lines of transgenic mice were made using 5 Kb of 5'-flanking control region of human CRF linked to a Neomycin Phosphotransferase II reporter. All four lines expressed the CRF transgene in hypothalamus, and three lines exhibited an appropriate induction in response to stress. These 3 lines were further examined, and exhibited regulation of the CRF transgene by the circadian rhythm, similar to the expression of endogenous CRF. This cycling of transgene expression was inhibited by dexamethasone, again similar to the well-characterized feedback regulation by glucocorticoids on endogenous CRF expression, a regulatory pattern which is restriced to the hypothalamus. In addition, male and female mice exhibited sexually dimorphic expression of the transgene, similar to that described and demonstrated for the endogenous CRF expression. It therefore appears that most, if not all, of the physiologic regulation of this complex CRF expression pattern is transcriptional.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1997
- Accession Number
- ADB236776
Entities
People
- Thiruvamoor P. Ramkumar
Organizations
- Washington University in St. Louis