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Corticotropin-releasing hormone

Corticotropin-releasing hormone (CRH), a neurohormone, is a large peptide consisting of a single chain of 41 amino acids. It stimulates not only secretion of corticotropin in the pituitary gland but also the synthesis of corticotropin in the corticotropin-producing cells (corticotrophs) of the anterior lobe of the pituitary gland. Many factors, both neurogenic and hormonal, regulate the secretion of CRH, since CRH is the final common element directing the body's response to all forms of stress, whether physical or emotional, external or internal. (This key role of CRH in the hypothalamic-pituitary-adrenal axis is discussed below in connection with the adrenal gland.) Among the hormones that play an important role in modulating the influence of CRH is cortisol, the major hormone secreted by the adrenal cortex, which, as part of the negative feedback servomechanism (exerting control over another system through negative feedback), blocks the secretion of CRH. Vasopressin, the major regulator of the body's excretion of water, has an additional ancillary role in stimulating the secretion of CRH.

Excessive secretion of CRH leads to an increase in the size and number of corticotrophs in the pituitary gland, often resulting in a pituitary tumour. This, in turn, leads to excessive stimulation of the adrenal cortex, resulting in high circulating levels of adrenocortical hormones, the clinical manifestations of which are known as Cushing's syndrome. Conversely, a deficiency of CRH-producing cells can, by a lack of stimulation of the pituitary and adrenal cortical cells, result in adrenocortical deficiency. (These conditions are discussed below.

Growth hormone-releasing hormone

Like CRH, growth hormone-releasing hormone (GHRH) is a large peptide. A number of forms have been described that differ from one another only in minor detail and in the number of amino acids (varying from 37 to 44). Unlike the other neurohormones, GHRH is not widely distributed in other parts of the brain. It is stimulated by stresses, including physical exercise, and secretion is blocked by a powerful inhibitor called somatostatin (see below Somatostatin). Negative feedback control of GHRH secretion is mediated largely through compounds called somatomedins, growth-promoting hormones that are generated when tissues are exposed to growth hormone itself.

An excess of circulating growth hormone in adults leads to a condition called acromegaly. Rarely, a benign tumour, called a hamartoma, located in the hypothalamus may produce excessive amounts of GHRH, leading to acromegaly. Equally rare are tumours arising in the islets of Langerhans of the pancreas that may secrete excessive quantities of GHRH. Indeed, GHRH was first successfully isolated and analyzed from such an ectopic (abnormally positioned) hormone-producing tumour. Isolated deficiency of GHRH (in which there is normal functioning of the hypothalamus except for this deficiency) may be the cause of one form of dwarfism, a general term applied to all individuals with abnormally small stature.
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