The functional neuroanatomy of corticotropin-releasing factor

Descriptions of the central distribution of corticotropin-releasing factor (CRF) have been taken as generally supporting the proposition that this neuropeptide is involved in the mediation of complementary neuroendocrine, autonomic and behavioural responses to stress. The hypothalamic paraventricular nucleus (PVN) is recognized as the principal source of CRF in hypophysial portal plasma; CRF mRNA and peptide expression in parvocellular neurosecretory neurons are regulated negatively by adrenal steroids and positively by many stressors. Consistent with the latter, the hypophysiotropic zone of the PVN receives a rich, and biochemically differentiated, afferent supply that provides visceral, somatic and special sensory systems with access to the 'CRF neuron'. Within the PVN, CRF is also expressed, and differentially regulated, in oxytocinergic magnocellular neurosecretory neurons and in autonomic-related projection neurons. CRF expression in at least some extrahypothalamic cell groups (olfactory bulb, Barrington's nucleus) is responsive to certain stressful stimuli, but not to perturbations of the steroid environment. Refinement of our understanding of the central distribution of CRF has been provided by the recognition that most CRF antisera cross-react with an amidated dipeptide encoded by the melanin-concentrating hormone precursor, and by the likelihood that some central sites of CRF peptide expression may be muted or masked by the presence of a CRF-binding protein (CRF-BP). The CRF-BP is expressed prominently in the telencephalon, where it is co-localized with CRF in some neurons, and in anterior pituitary corticotrophs.