ACTH also

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

Other Hormones. Pituitary hormones regulate the function of many other endocrine glands, and hypophysectomy in male rats results in a decrease in the activity of xenobiotic metabolizing enzymes. Administration of adrenocorticotropic hormone (ACTH) also results in a decrease of those oxidative enzyme activities that are gender dependent. In contrast, ACTH treatment of female rats causes an increase in aminopyrine /V-dcmcthylasc but no change in other activities. 

ACTH stimulates the adrenal cortex to produce glucocorticoids, mineralocorticoids, and androgens. ACTH increases the activity of cholesterol esterase, the enzyme that catalyzes the rate-limiting step of steroid hormone production cholesterol - pregnenolone. ACTH also stimulates adrenal hypertrophy and hyperplasia. When given chronically in pharmacologic doses, corticotropin causes increased skin pigmentation. 

The adrenal cortex releases Cortisol (CORT) depending on ACTH (also following Michaelis-Menten kinetics) and degrades with a time constant kcoRT ... 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

It was concluded from these and other studies in hypophysectomized animals that ACTH had no effect on aldosterone release. The volume-sensitive renal mechanism appears to be mainly responsible for postoperative aldosterone changes (S4), but it would now appear that ACTH also plays a part in regulating aldosterone secretion (S4). Removal of the pituitary leads to an immediate fall in aldosterone levels in adrenal venous blood (H9). A linear dose response relationship exists between the infusion rate of ACTH and aldosterone secretion rates (H9). Volume receptors in the right atrium and in the vascular tree respond to minor reductions in blood volume and play an important part in stimulating the aldosterone response (Bl, FI). Patients with suppression of cortisol production due to prolonged administration of steroids continue to secrete aldosterone and are able to increase their output after stress indicating the presence of another trophic factor as well as ACTH (T3). 

Adrenal Corticotropic Hormone (ACTH) (also called / -corticotropin) is a peptide hormone secreted by the anterior pituitary gland. ACTH stimulates the adrenal cortex to produce glucocorticoids and mineralocorticoids, which in turn act on a number of tissues (Figure 23.8). 

Most pituitary hormones act on endocrine glands that occupy an intermediate, or secondary, position in the hierarchy, stimulating them to produce hormones that exert the ultimate actions on target tissues. Pituitary hormones that act on other endocrine glands are called tropic hormones or tropins. An example is adrenal corticotropic hormone (ACTH), also called / -corticotropin (see here also). This peptide is secreted from the anterior pituitary, and it stimulates the adrenal cortex to produce glucocorticoids and mineralocorticoids, which in turn act on a number of tissues. 

For the treatment of suspected but unconfirmed acute adrenal insufficiency, 4 mg of dexam-ethasone sodium phosphate can be substituted for hydrocortisone, since dexamethasone does not cross-react in the cortisol assay and will not interfere with the measurement of cortisol (either basaUy or in response to the cosyntropin stimulation test). A failure to respond to cosyntropin in this setting is diagnostic of adrenal insufficiency. Often, plasma ACTH also is measured to provide information about the underlying etiology if the diagnosis of adrenocortical insufficiency is established. 

Synthesis The limbic system ultimately controls cortisone production by regulating release of corticotropin releasing hormone (CRH) from the hypothalamus via serotoninergic, dopaminergic and cholinergic neurons. CRH stimulates release of adreno-corticotrophic hormone (ACTH) from the anterior pituitary. ACTH activates adenylate cyclase in the adrenal cortex. The resulting cAMP activates protein kinase which enhances cholesterol esterase activity. Cholesterol esterase increases the amount of cholesterol available to mitochondria, where cortisone is made from cholesterol. ACTH also stimulates the conversion of cholesterol to pregnenolone, the first step in steroid synthesis. 

In addition to stimulating corticosteroidogenesis in the adrenals, ACTH also stimulates lipogenesis in adipose tissue and the release of ascorbic acid from the adrenals. 

The hormones chiefly responsible for coordinating the energy metabolism of the various tissues are glucagon, adrenaline and insulin noradrenaline and ACTH also play a part. All of them, except insulin, have the effect of raising the blood sugar level. 

ACTH- and USE peptides also act in dogs after adrenalectomj moreover, ACTH also retains its full activity when boiled in NaOH n/10. On the other hand, there is no clear correlation between the STS and the other known extra-adrenal effects of ACTH. 

Control of secretion of anterior pituitary hormones also includes inhibition by hormones produced by target organs. For example, CRH stimulates the anterior pituitary to secrete ACTH, which in turn stimulates the adrenal cortex to secrete corticosteroids. Corticosteroids then feed back to inhibit the secretion of ACTH. Feedback mechanisms are important for the control of most hormones. For example, insulin (qv) secretion from the pancreas increases in response to increased blood glucose resulting from ingestion of a meal. Insulin increases tissue uptake and metaboHsm of glucose, which lowers blood glucose and in turn reduces insulin secretion. 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

This section of the chapter discusses FSH, LH, GH, and ACTH. FSH and LH are called gonadotropins because they influence the gonads (the organs of reproduction). GH, also called somatotropin, contributes to the growth of the body during childhood, especially the growth of muscles and bones. ACTH is produced by the anterior pituitary and stimulates the adrenal cortex to secrete the corticosteroids. The anterior pituitary hormone, TSH, is discussed in Chapter 51. Prolactin, which is also secreted by the anterior pituitary, stimulates the production of breast milk in the postpartum patient Additional functions of prolactin are not well understood. Prolactin is the only anterior pituitary hormone that is not used medically. 

ACTH, adrenocorticotropic hormone or corticotropin FDA, Food and Drug Administration HPA, hypothalamic-pituitary-adrenal IV, intravenously. aThe 250 meg dose has also been administered intramuscularly in an outpatient setting. The 1 meg dose is not FDA-approved. 

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