title: Negative regulation of corticotropin releasing factor expression and limitation of stress response.
abstract: Corticotropin releasing factor (CRF) coordinates behavioral, autonomic and hormonal responses to stress. Activation of the hypothalamic pituitary adrenal (HPA) axis with stimulation of CRF and vasopressin (VP) release from hypothalamic parvocellular neurons, and consequent secretion of ACTH from the anterior pituitary and glucocorticoid from the adrenal cortex, is the major endocrine response to stress. Current evidence indicates that the main regulator of ACTH secretion in acute and chronic conditions is CRF, in spite of the fact that the selective increases in expression of parvocellular VP and pituitary VP V1b receptors observed during prolonged activation of the HPA axis have suggested that VP becomes the predominant regulator. Following CRF release, activation of CRF transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevation of CRF and glucocorticoid production. While glucocorticoid feedback plays an important role in regulating CRF expression, the relative importance of direct transcriptional repression of the CRF gene by glucocorticoids in the overall feedback mechanism is not clear. In addition to glucocorticoids, intracellular feedback mechanisms in the CRF neuron, involving induction of repressor forms of cAMP response element modulator (CREM) limit CRF transcriptional responses by competing with the positive regulator, phospho-CREB. Rapid repression of CRF transcription following stress-induced activation is likely to contribute to limiting the stress response and to preventing disorders associated with excessive CRF production.
authors.affiliation: Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-1103, USA. greti_aguilera@nih.gov
authors.forename: Greti
authors.initials: G
authors.lastname: Aguilera
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Anna
authors.initials: A
authors.lastname: Kamitakahara
mesh_terms: D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D051786:Cyclic AMP Response Element Modulator / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*
chemical_list: C497412:Crem protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D051786:Cyclic AMP Response Element Modulator; D003346:Corticotropin-Releasing Hormone