Adrenocorticotrophic hormone ACTH

As well as the sex hormones already mentioned (see above), many other hormones seem to affect the metabolism of foreign compounds and therefore may have effects on toxicity. A number of pituitary hormones may directly, as well as indirectly, affect metabolism, for example, growth hormone, follicle-stimulating hormone, adrenocorticotrophic hormone, luteinizing hormone, and prolactin. Thus, hypophysectomy in male rats results in a general decrease in metabolism, but the effects of some of the individual hormones may depend on the sex of the animal and the particular enzyme or metabolic pathway. For example, adrenocorticotrophic hormone (ACTH) administration decreases oxidative metabolism in males but increases N-demethylation in female rats. Removal of the adrenal gland reduces metabolism, such as ethylmorphine demethylation and aniline 4-hydroxylation, and this can... 

The adrenocorticotrophic hormone ACTH (corticotropin) stimulates the adrenal cortex to secrete the glucocorticoids hydrocortisone (cortisol) and corticosterone, the mineralocorticoid aldosterone, and a number of weakly androgenic substances, as well as a small amount of testosterone. Aldosterone synthesis is also regulated by renin and angiotensin. 

Pituitary activity is absolutely central to osmoregulation, and hypophy-sectomy destroys the ability of fish to adapt to a change in salinity. The prolactin is synthesized in, and is secreted by, the pituitary, which also secretes adrenocorticotrophic hormone (ACTH), which, in turn, stimulates the adrenals to produce cortisol. The level of ACTH in the plasma is therefore raised when fish are in sea water (Nichols and Fleming, 1990). The pituitary also secretes growth hormone into the blood plasma in sea water (Yada and Hirano, 1992 rainbow trout) but its role is not clear in the present context. 

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.

Figure 18.5. Endocrine-immune relationship following chronic stress. In chronic stress, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback control. Arginine vasopressin (AVP) is secreted from the hypothalamus and induces the release of adrenocorticotrophic 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. Unlike in acute stress, the negative feedback of cortisol to the hypothalamus and pituitary 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.

Rats on a pantothenic acid-free diet show rapid depletion of adrenal corticosteroids, and reduced production of the steroids in isolated adrenal glands in response to stimulation with adrenocorticotrophic hormone (ACTH). This presumably reflects the role of acetyl CoA in the synthesis of steroids deficiency also results in atrophy of the seminiferous mbules of male rats and delayed sexual maturation in females. As deficiency progresses, there is enlargement, then congestion, and finally hemorrhage, of the adrenal cortex. In young animals, but not in adults, pantothenic acid deprivation eventually leads to necrosis of the adrenal cortex. 

ADRENOCORTICOTROPHIC HORMONE (ACTH) ORIGIN Anterior pituitary gland (basophil cells) STRUCTURE Polypeptide... 

Two neuropeptides, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are released from parvoceUular neurons in the hypothalamic PVN to initiate a stress response. The terminal endings of these neurons, located in the median eminence of the hypothalamus, release CRH and AVP into the hypothalamic-hypophysial portal vessel system, where they travel to the anterior pituitary. The two neuropeptides act syn-ergistically on pituitary corticotrophs to activate the synthesis of pro-opiomelanocortin (POMC). This peptide, discussed in detail below, is processed to produce several peptides including adrenocorticotrophic hormone (ACTH), or corticotropin. ACTH released from corticotrophs travels via the bloodstream to act on cells in the zona fasciculata layer of the adrenal cortex, stimulating the synthesis and release of the glucocorticoids, cortisol (in humans) or corticosterone (in rodents). 

Corticotrophin-releasing hormone (CRH corticotrophin-releasing factor. CRF) controls release of corticotrophin (adrenocorticotrophic hormone. ACTH). which in turn controls the release of corticosteroids from the adrenal glands. See corticotrophin-releasing factor RECEPTOR agonists CORTICOTROPHIN-RELEASING FACTOR RECEPTOR ANTAGONISTS. 

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