MODULE SUPPLEMENT: ENDOCRINE SYSTEM
CRH, Adrenocorticotropic Hormone/Corticotropin (ACTH), and Cortisol

The hypothalamic-pituitary-adrenal axis is extremely important in the regulation of our response to many external and internal demands or stressors.

The Adrenal Glands are located just over and anterior to each kidney and are made up of two fairly distinct components: the cortex or outer layer and the medulla.

The Cortex has 3 layers

• Zona glomerulosa--outer--minerocorticoids (aldosterone)
• Zona Facicularis--middle--glucocorticoids (cortisol), adrenal androgens
• Zona reticularis--inner--adrenal androgens, glucocorticoids

The Medulla produces mainly Epinephrine (some norepinephrine).

The glucocorticoids that are secreted by the adrenal cortex exert widespread effects, including: increased glucose production, protein breakdown and fatty acid mobilization; and suppression of the immune response and inflammation. They have also been implicated in alterations in memory with age.

Although some data suggest cortisol levels may be higher in the evening in older vs. younger adults (Ferrari, Casarotti, et al., 2001; Seeman, Singer et al., 2001), basal levels of glucocorticoids are felt not to change significantly from youth to old age in humans. Both secretion and clearance rates appear to decrease proportionately, although some data suggest that these remain stable in healthy older adults (Timiras, 2003). The adrenal response to ACTH is also fairly well preserved, although some recent data suggest that there may be some reduced sensitivity (Giordano, DiVito, et al., 2001). Further, the circadian profile flattens (Carvalhaes-Neto, Ramos, et al., 2002; Ferrari, Casarotti, et al., 2001) and there may also be alterations in the circannual (yearly) rhythmicity of total cortisol and free cortisol. A summary of the changes that occur with age in the hypothalamic-pituitary-adrenal cortisolaxis with age, as listed below, emphasizes the current controversial state of the data but do suggest that the older adult has less reserve and may be less able to adapt to various physiologic and psychologic challenges.

• Plasma ACTH levels & Circadian rhythm: No significant change
• ACTH response to CRH stimulation: No significant change
• Cortisol response to ACTH stimulation: No significant change vs. diminished sensitivity
• Basal plasma cortisol levels: No significant change or some increase (increase found mainly in corticosterone in animals)
• Production and Clearance of cortisol: Decreased vs. possibly no significant change
• Feedback inhibition of the ACTH-CRH-Cortisol loop: Decreased sensitivity or no significant change