アドレノコルチコトロピン

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Danger

• 危険有害性情報

  H317：アレルギー性皮膚反応を起こすおそれ

  H332：吸入すると有害

  H334：吸入するとアレルギー、喘息または、呼吸困難 を起こすおそれ

  H361：生殖能または胎児への悪影響のおそれの疑い

• 注意書き

  P260：粉じん/煙/ガス/ミスト/蒸気/スプレーを吸入しないこ と。

  P280：保護手袋/保護衣/保護眼鏡/保護面を着用するこ と。

  P342+P311：呼吸に関する症状が出た場合：医師に連絡すること。

アドレノコルチコトロピン 化学特性,用途語,生産方法

• 解説

  略称ACTH．コルチコトロピンともいう．下垂体前葉ホルモンの一つ．ACTHは副腎皮質に作用して副じん皮質ホルモンの生成，分泌を促進することによりストレスを和らげる．生合成の際の前駆物質は，ストレスに対処するためのほかのホルモン(エンドルフィンやメラノトロピン(MSH))も含んでおり，POMC(proopiomelanocortin，図)とよばれている．

• 生理機能

  アドレノコルチコトロピンは，ACTHは副腎に作用し，糖質コルチコイドの分泌を促進することにより間接的に糖代謝を調節するとともに，副腎以外の組織にも作用し，脂質代謝や糖代謝の制御を行っている．一部で，MSHと同一アミノ酸配列をもつためにMSH作用をもっている(図)．さらにコルチコイドの分泌促進作用による抗炎症作用もみられている．種差共通のN末端部1～24番目のアミノ酸ACTHの合成品は化学的に純粋であり，アレルギー，アナフィラキシーなどの副作用がないので，副腎皮質機能検査，副腎皮質ステロイド剤の減量，離脱などに用いられている．

• 効能

  診断薬(副腎皮質機能不全), メラノコルチン2受容体作動薬

• 説明

  Natural corticotropin is a 39-amino-acid polypeptide secreted by the anterior pituitary gland; it is obtained from animal pituitaries. The physiological activity resides in the first 24 amino acids (which are common to many species) and most immunological activity lies in the remaining 15 amino acids. The pituitary output of corticotropin responds rapidly to physiological requirements by the familiar negativefeedback homeostatic mechanism. As the t½ of corticotropin is 10 min and the adrenal cortex responds within 2 min, corticosteroid output can adjust rapidly.
  Synthetic corticotropins have the advantage of shorter amino acid chains (they lack amino acids 25–39) which are less likely to cause serious allergy, although this does occur. Additionally, they are devoid of animal proteins, which are potent allergens. Tetracosactide (tetracosactrin) consists of the biologically active first 24 amino acids of natural corticotropin (from humans or animals) and so it has similar properties, e.g. t½ 10 min.

• 使用

  Hormone (adrenocorticotropic); glucocorticoid; diagnostic aid (adrenocortical insufficiency) Acthar (Sanofi Aventis); Cortrophin (Organon) [Name previously used: Corticotrophin].

• 定義

  ChEBI: A polypeptide hormone produced and secreted by the pituitary gland comprising 39 amino acid residues coupled in a linear sequence. The N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic act vity. Corticotropin stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also sex steroids (androgens). It is used in the treatment of certain neurological disorders such as infantile spasms and multiple sclerosis, and diagnostically to investigate adrenocortical insufficiency.

• 適応症

  Corticotropin (ACTH, Acthar, Cortrophin Gel) is an open-chain polypeptide that consists of 39 amino acid residues, the first 24 of which are essential for its biological activity. The remainder of the amino acids are also clinically important, since they may be involved in stimulating antibody formation and causing allergic reactions. This is true especially when corticotropin of animal origin is injected into humans. Commercially available corticotropin is prepared from animal pituitary glands.

• 生物活性

  ACTH is the adrenocorticotropic hormone of the anterior lobe of the pituitary gland, which specifically stimulates the adrenal cortex to secrete cortisone, and hence has effects identical with those of cortisone. ACTH differs in its chemistry, absorption, and metabolism from the other adrenal steroids. Chemically, it is a watersoluble polypeptide having a molecular weight of about 3500. Its complete amino acid sequence has been determined. It produces its peripheral physiological effects by causing discharge of the adrenocortical steroids into the circulation. ACTH has been extracted from pituitary glands. In purified form, ACTH is useful in treating some forms of arthritis, lupus erythematosus, and severe skin disorders. The action of ACTH injections parallels the result of large quantities of naturally formed cortisone if they were released naturally.

• 作用機序

  Corticotropin stimulates the synthesis of corticosteroids (of which the most important is cortisol) and to a lesser extent of androgens, by the cells of the adrenal cortex. It has only a minor (transient) effect on aldosterone production, which proceeds independently; in the absence of corticotropin the cells of the inner cortex atrophy.
  The release of natural corticotropin by the pituitary gland is controlled by the hypothalamus through corticotropin releasing hormone (CRH, or corticoliberin), production of which is influenced by environmental stresses as well as by the level of circulating cortisol. High plasma concentration of any adrenal steroid with glucocorticoid effect prevents release of CRH and so of corticotropin, lack of which in turn results in adrenocortical hypofunction. This is why catastrophe may accompany abrupt withdrawal of long-term adrenal steroid therapy with adrenal atrophy.
  The effects of corticotropin are those of the steroids (hydrocortisone, androgens) liberated by its action on the adrenal cortex. Prolonged heavy dosage causes the clinical picture of Cushing's syndrome.

• 薬理学

  Corticotropin is rapidly inactivated by gastrointestinal proteolytic enzymes and therefore must be administered parenterally. It is rapidly removed from the circulation (T_1/2, 15 minutes) and is probably inactivated in body tissues, since no intact compound is found in the urine.

• 臨床応用

  Corticotropin is used principally in diagnosis and rarely in treatment. It is inactive if taken orally and has to be injected like other peptide hormones.
  Diagnostic use is to test the capacity of the adrenal cortex to produce cortisol. With the short synacthen test, the plasma cortisol concentration is measured before and 30 min and 60 min after an intramuscular injection of 250 micrograms of tetracosactide (Synacthen); a normal response is a rise in plasma cortisol concentration of more than 200 nmol/L or a peak of greater than 500 nmol/L at 30 or 60 min. In cases of uncertainty, the longer variants of the test require intramuscular injection of a depot (sustained-release) formulation, e.g. 1 mg daily for 3 days at 09:00 hours, with a short tetracosactide test performed on day 3.
  Therapeutic use is seldom appropriate, as the peptide hormone must be injected. Selective glucocorticoid (without mineralocorticoid) action is not possible, and clinical results are irregular. Corticotropin cannot be relied on to restore adrenal cortisol output when a steroid is being withdrawn after prolonged therapy, as it does not restore function in the suppressed hypothalamic–pituitary part of the HPA axis.

• 副作用

  Aside from hypersensitivity and allergic reactions, corticotropin administration has been associated with electrolyte disturbances and masculinization in women.

• 概要

  副腎皮質刺激ホルモン．脳下垂体前葉で産生される．ウシ：Glu33→Gln，ヒツジ：Asn25→Asp，Glu33→Gln，ブタ：Ser31→Leu

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