Corticotropin-releasing hormone actions

The action of HA is indirect, mediated primarily via activation of corticotropin-releasing hormone (CRH) originating in parvocellular neurons in the PVN and secondly via vasopressin (AVP) originating in parvo- and magnocellular neurons in the PVN and in the SON [18-24]. The effect of CRH is predominantly mediating in character (i.e. HA releases CRH which subsequently stimulates ACTH secretion) [18] while the effect of AVP seem to be mediating as well as permissive in character (i.e. AVP has to be present in order for HA to exert its effect on ACTH secretion) [25]. Besides these two important mediators, prostaglandins are involved in HA-induced release of the POMC-derived peptides from the anterior lobe [26], whereas catecholamines, oxytocin (OT) and serotonin (5-HT) do not participate [27-28, Willems et al. (unpublished observations)]. 

Corticotropin (corticotrophin adrenocorticotrophin ACTH) is a straight-chain polypeptide with39 amino acid residues, and its function is to control the activity of the adrenal cortex, particularly the production of corticosteroids. Secretion of the hormone is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH was formerly used as an alternative to corticosteroid therapy in rheumatoid arthritis, but its value was limited by variable therapeutic response. ACTH may be used to test adrenocortical function. It has mainly been replaced for this purpose by the synthetic analoguetetracosactide (tetracosactrin) (Figure 7.10), which contains the first 24 amino acid residues of ACTH, and is preferred because of its shorter duration of action and lower allergenicity. 

Secretion and actions of adrenocorticotropic hormone (ACTH). CRH, corticotropin-releasing hormone. 

Karalis K, Sano H, Red wine J, Listwak S, Wilder RL, Chrousos GP (1991) Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science 254 421 23. 

Use in diagnosis dexamethasone suppression test. Dexamethasone acts on the h5q othalamus (like hydrocortisone), to reduce output of corticotropin releasing hormone (CRH), but it does not interfere with measurement of corticosteroids in blood or urine. Normal suppression of cortisol production after administering dexamethasone indicates that the hypothalamic/pituitary/adrenal axis is intact. Failure of suppression implies pathological hypersecretion of ACTH by the pituitary or of cortisol by the adrenal. Dexamethasone is used because its action is prolonged (24 h). There are several ways of carrying out the test. 

ACTH is the smallest of the hormones produced by the anterior pituitary. It is synthesized in the y-cells when they are stimulated by corticotropin releasing hormone (see Releasing hormones). The target organ of ACTH is the adrenal cortex, which it stimulates to growth and increased production of glucocorticoids, an action mediated by adenylate cyclase. 

Secretion of adrenocortical steroids is controlled by the pituitary release of corticotropin (ACTH). Secretion of the salt-retaining hormone aldosterone is primarily under the influence of angiotensin. Corticotropin has some actions that do not depend on its effect on adrenocortical secretion. However, its pharmacologic value as an anti-inflammatory agent and its use in testing adrenal function depend on its secretory action. Its pharmacology is discussed in Chapter 37 and is reviewed only briefly here. 

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