Cortisol, release from pituitary-adrenal axis

Corticotropin-releasing factor and arginine vasopressin, which are released predominantly by the paraventricular nucleus of the hypothalamus, are important regulators of corticotropin (ACTH) release, which in turn triggers the release of cortisol and other steroids by the adrenal gland. Both the administration of certain psychoactive agents and emotional arousal originating from the limbic system are able to modify the functions of the pituitary-adrenal axis and stimulate the synthesis of cortisol. 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

Secondary adrenal insufficiency most commonly results from exogenous corticosteroid use, leading to suppression of the hypothalamic-pituitary-adrenal axis and decreased release of ACTH, resulting in impaired androgen and cortisol production. Mirtazapine and progestins (e.g., medroxyprogesterone acetate, megestrol acetate) have also been reported to induce secondary adrenal insufficiency. Secondary disease typically presents with normal mineralocorticoid concentrations. 

ACTH adrenocorticoh ophic hormone is a peptide hormone released by anterior pituitary cells in response to shessful stimuli that causes the synthesis and release of cortisol (corticosteroid) from the adrenal cortex. It is an important component of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH is released from pro-opiomelanocortin and secreted from corticotropes in response to corticotropin-releasing hormone (CRH) released by the hypothalamus. 

Also, since the hypothalamic-pituitary-adrenal axis (HPA) of the fetus in E+ mares appears to be compromised and results in prolonged gestation lengths in mares, and the associated problems thereof, domperidone may be having some effect on the HPA system since mares receiving domperidone while grazing E+ fescue foal at or near their expected foaling date with normal, healthy foals. And, since ACTH levels in foals from E+ mares are low, and ACTH is the stimulus for adrenal cortisol release and since normal fetal adrenal cortisol levels appear to be... 

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop that includes the hypothalamus, the pituitary and the adrenal glands. The main hormones that activate the HPA axis are corticotrophin releasing factor (CRF), arginine vasopressin (AVP) and adrenocorticotrophic hormone (ACTH). The loop is completed by the negative feedback of cortisol on the hypothalamus and pituitary. The simultaneous release of cortisol into the circulation has a number of effects, including elevation of blood glucose for increased metabolic demand. Cortisol also negatively affects the immune system and prevents the release of immunotransmitters. Interference from other brain regions (e.g. hippocampus and amygdala) can also modify the HPA axis, as can neuropeptides and neurotransmitters.

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