Central and feedback regulation of hypothalamic corticotropin-releasing factor secretion

Physical, emotional and metabolic stressors activate the hypothalamo-pituitary-adrenal (HPA) axis via multiple neural pathways. Final hypothalamic coding of stressor-induced adrenocorticotropic hormone (ACTH) secretion is mediated by differential release of ACTH secretagogues. These include, but may not be limited to, corticotropin-releasing factor (CRF), arginine vasopressin, oxytocin and, possibly, adrenaline. Among these substances, CRF serves as the predominant regulatory factor of this axis because its presence is obligatory for the action of intrinsically weaker secretagogues. Because neural input-encoding qualities of individual stressors utilize, in part, stimulus-specific pathways, the effectiveness of glucocorticoid negative feedback in modulating ongoing and subsequent activity of the HPA axis is dependent upon the type of stressor and the nature of the neural pathways mediating the initial activity. Studies suggest that responses to physical stressors (for example, haemorrhage) are resistant to classical intermediate feedback, whereas those to emotional/cognitive stressors (such as a novel environment) are strongly susceptible to feedback. Overall functional characteristics of the HPA axis in adult organisms are at least partially a result of neonatal experience. In the adult differences in hypothalamic CRF mRNA levels, median eminence peptide content and pituitary responsiveness to stressors can be correlated with aspects of neonatal experience.