WordNet

hormone that is one of the steroids of the adrenal cortex that influences the metabolism of sodium and potassium

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/17 15:27:05」(JST)

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Aldosterone

Deoxycorticosterone

Fludrocortisone

Mineralocorticoids are a class of steroid hormones characterized by their influence on salt and water balances. The primary mineralocorticoid is aldosterone.

Physiology[edit]

The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium, a mineral. The primary endogenous mineralocorticoid is aldosterone, although a number of other endogenous hormones (including progesterone and deoxycorticosterone) have mineralocorticoid function.

Aldosterone acts on the kidneys to provide active reabsorption of sodium and an associated passive reabsorption of water, as well as the active secretion of potassium in the principal cells of the cortical collecting tubule and active secretion of protons via proton ATPases in the lumenal membrane of the intercalated cells of the collecting tubule. This in turn results in an increase of blood pressure and blood volume.

Aldosterone is produced in the cortex of the adrenal gland and its secretion is mediated principally by angiotensin II but also by adrenocorticotrophic hormone (ACTH) and local potassium levels.

Mode of action[edit]

The effects of mineralocorticoids are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades.

Steroidogenesis, showing mineralocorticoids in ellipse at top right. Note that it is not a strictly bounded group, but a continuum of structures with increasing mineralocorticoid effect, with the primary example aldosterone at top.

Genomic mechanisms[edit]

Mineralocorticoids bind to the cytosolic mineralocorticoid receptor. This type of receptor gets activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many hormone response elements (HREs) in the promoter region of the target genes in the DNA.

The opposite mechanism is called transrepression. The hormone receptor without ligand binding interacts with heat shock proteins and prevents the transcription of targeted genes.

Aldosterone and cortisol (a glucosteroid) have similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids. This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a condition known as pseudohyperaldosteronism.^[1]

Pathophysiology[edit]

Hyperaldosteronism (the syndrome caused by elevated aldosterone) generally results from adrenal cancers. The two main resulting problems:

Hypertension and edema due to excessive Na+ and water retention.
Accelerated excretion of potassium ions (K+). With extreme K+ loss there is muscle weakness and eventually paralysis.

Underproduction, or hypoaldosteronism, leads to the salt-wasting state associated with Addison's disease, although classical congenital adrenal hyperplasia and other disease states may also cause this situation.

Pharmacology[edit]

An example of a synthetic mineralocorticoid is fludrocortisone (Florinef). Important mineralocorticoid inhibitors are spironolactone and eplerenone.

References[edit]

Stewart P (2008): "The Adrenal Cortex " In: Kronenberg, Melmed, Polonsky, Larsen (eds.) Williams Textbook of Endocrinology (11 ed)., Saunders Elsevier, Philadelphia, pp.445-504.
Bennett PN and Brown MJ (2008) “Adrenal corticosteroids, antagonists, corticotropin”, in Clinical Pharmacology (10ed), Churchill Livingstone Elsevier, Publ. pp. 593-607.
Hu X, Funder JW (2006) The evolution of mineralocorticoid receptors. Mol Endocrinol. 20(7):1471-8.
McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. (2006) International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev. Dec;58(4):782-97.
Pippal JB, Fuller PJ. (2008) Structure-function relationships in the mineralocorticoid receptor. J Mol Endocrinol. 41(6):405-13.

^ Omar, HR; Komarova, I; El-Ghonemi, M; Fathy, A; Rashad, R; Abdelmalak, HD; Yerramadha, MR; Ali, Y; Helal, E; Camporesi, EM (2012). "Licorice abuse: Time to send a warning message". Therapeutic Advances in Endocrinology and Metabolism 3 (4): 125–138. doi:10.1177/2042018812454322. PMC 3498851. PMID 23185686.

UpToDate Contents

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1. 成人における副腎不全の治療 treatment of adrenal insufficiency in adults
2. 見かけの鉱質コルチコイド過剰（AME）症候群（長期甘草摂取を含む） apparent mineralocorticoid excess syndromes including chronic licorice ingestion
3. まれな先天性副腎過形成 uncommon congenital adrenal hyperplasias
4. 小児における副腎不全の治療 treatment of adrenal insufficiency in children
5. 低レニン性原発性（本態性）高血圧 low renin primary essential hypertension

English Journal

Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma.

Fernandes-Rosa FL1, Williams TA1, Riester A1, Steichen O1, Beuschlein F1, Boulkroun S1, Strom TM1, Monticone S1, Amar L1, Meatchi T1, Mantero F1, Cicala MV1, Quinkler M1, Fallo F1, Allolio B1, Bernini G1, Maccario M1, Giacchetti G1, Jeunemaitre X1, Mulatero P1, Reincke M1, Zennaro MC2.
Hypertension.Hypertension.2014 Aug;64(2):354-61. doi: 10.1161/HYPERTENSIONAHA.114.03419. Epub 2014 May 27.
Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA
PMID 24866132

Inhibition of the androgen receptor by mineralocorticoids at levels physiologically achieved in serum in patients treated with abiraterone acetate.

Kim W1, Jones JO2, Diamond M3, Haqq C4, Molina A5, Small EJ1, Ryan CJ1.
Prostate cancer and prostatic diseases.Prostate Cancer Prostatic Dis.2014 Jul 22. doi: 10.1038/pcan.2014.27. [Epub ahead of print]
Background:Abiraterone acetate (AA), a highly potent CYP17A1 inhibitor, has demonstrated marked clinical benefit in patients with metastatic castration-resistant prostate cancer (CRPC). Phase I trials of AA without prednisone showed significant elevation of serum mineralocorticoid concentrations. Th
PMID 25047002

Addison's Disease and Pituitary Enlargement.

Winters SJ1, Vitaz T, Nowacki MR, Craddock DC, Silverman C.
The American journal of the medical sciences.Am J Med Sci.2014 Jul 7. [Epub ahead of print]
: A 60-year-old man with Addison's disease, primary hypothyroidism and type 2 diabetes mellitus who was treated with stable doses of hydrocortisone and fludrocortisone developed increasing skin pigmentation and a bitemporal hemianopia. The plasma ACTH level was 14,464 pg/mL, and an invasive pituitar
PMID 25004119

Japanese Journal

Blood Pressure Variability Activates Cardiac Mineralocorticoid Receptor and Induces Cardiac Remodeling in Hypertensive Rats

YASUOKA Suguru,KAI Hisashi,KAJIMOTO Hidemi,KUDO Hiroshi,TAKAYAMA Narimasa,ANEGAWA Takahiro,KOGA Mitsuhisa,MIYAMOTO Takanobu,MIFUNE Hiroharu,KAGE Masayoshi,HIROOKA Yoshitaka,IMAIZUMI Tsutomu
Circulation journal : official journal of the Japanese Circulation Society 77(6), 1474-1481, 2013-05-25
NAID 10031158877

Molecular cloning and characterization of the corticoid receptors from the American alligator

Oka Kaori,Kohno Satomi,Urushitani Hiroshi,Guillette Louis J. Jr.,Ohta Yasuhiko,Iguchi Taisen,Katsu Yoshinao
Molecular and Cellular Endocrinology 365(2), 153-161, 2013-01-30
… Although extensively studied in mammals and some non-mammalian species, the molecular mechanisms of corticosteroid hormone (glucocorticoids and mineralocorticoids) action are poorly understood in reptiles. …
NAID 120005228364

Blood Pressure Variability Activates Cardiac Mineralocorticoid Receptor and Induces Cardiac Remodeling in Hypertensive Rats

Yasuoka Suguru,Kai Hisashi,Kajimoto Hidemi,Kudo Hiroshi,Takayama Narimasa,Anegawa Takahiro,Koga Mitsuhisa,Miyamoto Takanobu,Mifune Hiroharu,Kage Masayoshi,Hirooka Yoshitaka,Imaizumi Tsutomu
Circulation Journal 77(6), 1474-1481, 2013
Background: Hypertensive patients with large blood pressure variability (BPV) have aggravated target organ damage. Because the aldosterone/mineralocorticoid receptor (MR) system is a possible mechanis …
NAID 130003361669

Related Pictures

secrete 1 outer zone mineralocorticoids CHRONIC ADRENOCORTICAL INSUFFICIENCY. too many mineralocorticoids in the blood Treating Dogs with Hypoadrenocorticism Changes in pituitary function with ageing to measure levels of mineralocorticoids Monogenic Forms of Low-Renin Hypertension Addison’s disease