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Development of the Hypothalamic‐Pituitary‐Adrenal Axis and the Stress Response

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The sections in this article are:

1 Ontogeny of the Hypothalamic‐Pituitary‐Adrenal Axis
1.1 Hypothalamic Paraventricular Nucleus
1.2 Pituitary Function
1.3 Adrenal Function
1.4 Glucocorticoid Feedback
1.5 Hypothalamic‐Pituitary‐Adrenal Function and Stress Responsiveness in Development
2 Conclusions
Figure 1. Figure 1.

Control of the activity of the hypothalamic‐pituitary‐adrenal (HPA) axis by internal and external sensory inputs. Sensory information from the oral cavity and the thoracic and abdominal viscera is carried to the brain stem via the glossopharyngeal and vagus nerves, with other inputs conveyed by the dorsal roots. Brain stem inputs to the hypothalamic paraventricular nucleus (PVN) stimulate secretion of corticotropin‐releasing factor (CRF) and other corticotropin (ACTH) secretagogues (including arginine vasopressin, AVP) into the hypophysial portal circulation. Other inputs to the hypothalamic PVN neurons are provided by the corticolimbic circuit (prefrontal cortex, hippocampus, bed nucleus of the stria terminalis, amygdala) and humoral signals of central and/or peripheral origin. Upon CRF and AVP stimulation, pituitary corticotropes secrete corticotropin in the peripheral circulation, which stimulates corticoster‐oidogenesis and release of glucocorticoids. These steroids limit the activity of the HPA axis by acting at multiple levels (pituitary, hypothalamic, and extrahypothalamic) to inhibit CRF and corticotropin production. The biological activity of glucocorticoids is regulated by their clearance rate as well as by the production of corticosterone‐binding globulin (CBG) from the liver. During development, tight control over glucocorticoid production is critical because of the important role of these steroids in central nervous system and peripheral maturational processes. ADR MED, adrenal medulla; ADR CTX, adrenal cortex; AP, anterior pituitary; PP, posterior pituitary.

Figure 1.

Control of the activity of the hypothalamic‐pituitary‐adrenal (HPA) axis by internal and external sensory inputs. Sensory information from the oral cavity and the thoracic and abdominal viscera is carried to the brain stem via the glossopharyngeal and vagus nerves, with other inputs conveyed by the dorsal roots. Brain stem inputs to the hypothalamic paraventricular nucleus (PVN) stimulate secretion of corticotropin‐releasing factor (CRF) and other corticotropin (ACTH) secretagogues (including arginine vasopressin, AVP) into the hypophysial portal circulation. Other inputs to the hypothalamic PVN neurons are provided by the corticolimbic circuit (prefrontal cortex, hippocampus, bed nucleus of the stria terminalis, amygdala) and humoral signals of central and/or peripheral origin. Upon CRF and AVP stimulation, pituitary corticotropes secrete corticotropin in the peripheral circulation, which stimulates corticoster‐oidogenesis and release of glucocorticoids. These steroids limit the activity of the HPA axis by acting at multiple levels (pituitary, hypothalamic, and extrahypothalamic) to inhibit CRF and corticotropin production. The biological activity of glucocorticoids is regulated by their clearance rate as well as by the production of corticosterone‐binding globulin (CBG) from the liver. During development, tight control over glucocorticoid production is critical because of the important role of these steroids in central nervous system and peripheral maturational processes. ADR MED, adrenal medulla; ADR CTX, adrenal cortex; AP, anterior pituitary; PP, posterior pituitary.

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Claire‐Dominique Walker, K.J.S. Anand, PAUL M. Plotsky. Development of the Hypothalamic‐Pituitary‐Adrenal Axis and the Stress Response. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 237-270. First published in print 2001. doi: 10.1002/cphy.cp070412