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Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balance. A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water Salt is a Dietary mineral composed primarily of Sodium chloride that is essential for Animal life but toxic to most land plants

Contents

Physiology

The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium, a mineral. Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 A mineral is a naturally occurring substance formed through geological processes that has a characteristic chemical composition a highly ordered atomic structure and specific The primary endogenous mineralocorticoid is aldosterone, although a number of other endogenous hormones (including progesterone and deoxycorticosterone) have mineralocorticoid function. The word endogenous means "arising from within" the opposite of Exogenous. Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water Progesterone is a C-21 Steroid Hormone involved in the Female Menstrual cycle, Pregnancy (supports Gestation Deoxycorticosterone (DOC is a Steroid hormone produced by the Adrenal gland that possess Mineralocorticoid activity and acts as a precursor

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. Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Water is a common Chemical substance that is essential for the survival of all known forms of Life. Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 In the Kidney, the collecting tubule ( CNT, or junctional tubule, or arcuate renal tubule) is a tubular segment of the renal Collecting duct The proton ( Greek πρῶτον / proton "first" is a Subatomic particle with an Electric charge of one positive ATPases are a class of Enzymes that catalyze the Decomposition of Adenosine triphosphate (ATP into Adenosine diphosphate (ADP and The collecting duct system of the Kidney consists of a series of tubules and ducts that connect the Nephrons to the Ureter. In the Kidney, the collecting tubule ( CNT, or junctional tubule, or arcuate renal tubule) is a tubular segment of the renal Collecting duct This in turn results in an increase of blood pressure and blood volume. Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Blood volume is the Volume of Blood (both Red blood cells and plasma) in a person's Circulatory system.

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. In Mammals the adrenal glands (also known as suprarenal glands) are the triangle-shaped Endocrine glands that sit on top of the Kidneys their Angiotensin causes blood vessels to constrict and drives blood pressure up Adrenocorticotropic hormone ( ACTH or corticotropin) is a Polypeptide Hormone produced and secreted by the Pituitary gland Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39

Mode of Action

Mineralocorticoids bind to the cytosolic mineralocorticoid receptor. The mineralocorticoid receptor (or MR MLR MCR also called Aldosterone receptor, is officially labelled Nuclear receptor subfamily 3 group C member This type of receptor gets activated upon ligand binding. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex tes itself into the cell nucleus, where it binds to many hormone response elements (HRE) in the promoter region of the target genes in the DNA. The term complex in Chemistry is usually used to describe molecules or ensembles formed by the combination of Ligands and metal Ions. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed A hormone response element (HRE is a Response element for Hormones, a short sequence of DNA within the Promoter of a gene that is able to bind In Biology, a promoter is a region of DNA that facilitates the transcription of a particular Gene. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known

The opposite mechanism is called transrepression. For other uses see Repression A repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing The hormone receptor without ligand binding interacts with heat shock proteins and prevents the transcription of targeted genes. A Hormone receptor is a Receptor protein on the surface of a cell or in its interior that binds to a specific Hormone. Heat shock proteins ( HSP) are a group of Proteins whose expression is increased when the cells are exposed to elevated temperatures or other stress Transcription is the synthesis of RNA under the direction of DNA

Aldosterone and cortisol have similar affinity for the mineralocorticoid receptor however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. Cortisol is a Corticosteroid Hormone produced by the Adrenal gland (in the Zona fasciculata of the Adrenal cortex) 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. Hydroxysteroid (11-beta dehydrogenase 2, also known as HSD11B2, is a human Gene. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a condition known as pseudohyperaldosteronism. Liquorice (UK or licorice (US (see spelling differences;, or) is the root of Glycyrrhiza glabra, from which a sweet flavour can be extracted Pseudohyperaldosteronism is a condition caused by the chronic excessive ingestion of Licorice.

18 hydroxy 11 deoxycorticosterone (also designated 18OH-DOC) is a steroid hormone probably used to conserve sodium and stimulate hydrogen ion (or acid) excretion. Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Hydrogen ion is recommended by IUPAC as a general term for all Ions of Hydrogen and its Isotopes Depending on the Charge of the ion 18OH-DOC lowers urine pH but has no affect on potassium excretion. Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 [1] This would seem to indicate that 18OH-DOC's primary purpose is to stimulate hydrogen ion or ammonium excretion. Ammonium is also an old name for the Siwa Oasis in western Egypt. Under low sodium intake 18 OH DOC is increased in serum. [2] There is a marked increase in serum 18OH DOC after injection of insulin [3] [4] and this may be due to the hypokalemic (low serum potassium) tendency after a rise in insulin [5] which in turn would make the serum more acidic. Hypokalemia refers to the condition in which the concentration of Potassium in the blood is low Since 18OH-DOC lowers urine pH (increases acidity) but has no affect on potassium excretion, this would seem to indicate that 18OH-DOC's primary purpose is to stimulate hydrogen ion or ammonium excretion. Its use by the body to conserve potassium would be indirect by virtue of hydrogen ion's interference with potassium excretion. [6] This interference is further indicated because injecting sodium bicarbonate or even hyperventilating (breathing rapidly beyond need) can triple potassium excretion. [7] The daily rhythm for potassium and hydrogen ion excretion show a rather close inverse relationship,[8] which gives additional circumstantial support to the supposition that they compete at a common site. 18OH-DOC is strongly dependent on the potassium cell or plasma content, because in potassium deficient rats markedly less 18OH-DOC is converted to 18OH-corticosterone and less yet if sodium is deficient. [9]

ACTH (a peptide hormone) has a large affect on 18OH DOC, causing 18OH DOC to go down to zero when ACTH does. Adrenocorticotropic hormone ( ACTH or corticotropin) is a Polypeptide Hormone produced and secreted by the Pituitary gland [10] This could be for the primary purpose of keeping serum immune enzymes and cell fluids at a high pH (alkaline) during internal infection, but not doing so during the intestinal infection of diarrhea, during which disease the resulting dehydration forces ACTH to decline. pH is the measure of the acidity or alkalinity of a Solution. [11] It probably is important normally to keep the vacuoles where pathogens are digested at a high pH because if the pH or alkalinity is not high enough, the pathogens inside the immune cells are not digested [12] and thus released intact. So when an intestinal disease is not calling for ACTH to decline, the indirect potassium conserving attribute of 18OH-DOC by virtue of stimulating acid excretion would be valuable, as would also increased acid excretion during internal disease be valuable.

18OH DOC may act primarily by blocking aldosterone's effect on potassium, and must have aldosterone to assist it with sodium. Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water Nichols, et al, have been able to show that injection of 18OH-DOC, which raised blood levels of this hormone ten times, were more retentive of sodium than a similar amount of aldosterone. So there must be a synergism involved. At the same time, the ratio of sodium to potassium excretion declined very little for 18OH-DOC, while for aldosterone, the ratio fell to as little as 1/3 that of control men. [13] This implies a considerable sparing of potassium by 18OH-DOC. Urine potassium excretion is not altered by 18OH-DOC injection. [14]

Angiotensin II has very little effect on 18OH-DOC and is ambiguous nor does serum potassium above 4. 8 mEq/litter (187 mg). [15] This last is not surprising since 18OH-DOC should not be used by the body at high serum potassium. Under low sodium intake, 18OH-DOC rises in the serum. [16] ACTH causes a marked increase in 18OH-DOC,[17] probably by a generalized affect on the zona fasciculata of the adrenal cortex where 18OH-DOC is synthesized. Cells of the zona fasciculata sit directly beneath the Zona glomerulosa and are organized in bundles (or Fascicles) Situated along the perimeter of the Adrenal gland, the adrenal cortex mediates the stress response through the production of Mineralocorticoids and Glucocorticoids So when it is necessary for sodium to be unloaded during the dehydration induced decline of ACTH [18] during diarrhea in order to preserve osmotic pressure, the resulting 18OH-DOC decline would assist in this.

18OH-DOC is deeply involved in one of the three forms (at least) of hypertension [19](high blood pressure). Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated

Pathophysiology

Hyperaldosteronism (the syndrome caused by elevated aldosterone) generally results from adrenal neoplasms. Hyperaldosteronism, also aldosteronism, is a Medical condition where too much Aldosterone is produced by the Adrenal glands, which can lead to The two main resulting problems:

  1. Hypertension and edema due to excessive Na+ and water retention. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling
  2. Accelerated excretion of potassium ions. Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 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. Addison's disease (also known as chronic Adrenal insufficiency, '''hypocortisolism''' or '''hypocorticism) is a rare Endocrine disorder Congenital adrenal hyperplasia ( CAH) refers to any of several Autosomal Recessive Diseases resulting from Mutations

Pharmacology

An example of synthetic mineralocorticoids is fludrocortisone (Florinef). Fludrocortisone is a synthetic Corticosteroid with moderate Glucocorticoid potency and much greater Mineralocorticoid potency Important mineralocorticoid inhibitors are spironolactone and eplerenone. Spironolactone (marketed under the trade names Aldactone, Novo-Spiroton, Spiractin, Spirotone, Verospiron or Berlactone Eplerenone ( INN) (ɛpˈlɛrənoʊn is an Aldosterone antagonist used as an adjunct in the management of Chronic heart failure.

Notes

  1. ^ Damasco MC Diaz F Anal JP Lantos CP 1979 Acute effects of three natural corticosteroids on the acid-base and electrolyte composition of urine in adrenalectomized rats. Acta Physiol. Latin Am. 29; 305.
  2. ^ Williams GH Braley LM Underwood RH 1976 The regulation of plasma 18 hydroxy 11-deoxycorticosterone in man. Journal of Clinical Investigation 58; 221-231.
  3. ^ Sparano F et al 1978 18-hydroxy-11-deoxycorticosterone response to insulin in normal man. Journal of Steroid Biochemistry 9; 1061–1063.
  4. ^ Hiatt N et al 1972 The effect of potassium chloride infusion on insulin secretion in vivo. Hormone Metabolism Research 4; 64.
  5. ^ Flatman JA & Clausen T 1979 Combined effects of adrenaline and insulin on active electrogenic Na+ and K= transport in rat soleus muscle. Nature 281 ; 580-581.
  6. ^ Berliner RW et al`1951 Relationship between acidification of the urine and potassium metabolism. American Journal Med. 11;274.
  7. ^ Kilburn KH 1966 Movements of potassium during acute respiratory acidosus and recovery. Journal of Applied Physiology 21; 679.
  8. ^ Mills JH & Stanbury SW 1954 A reciprocal relationship between K+ and H+ excretion in the diurnal excretory rhythm in man. Clinical Sci. 13; 172.
  9. ^ Muller J 1979 11beta hydroxylation of 18 – hydroxy – 11 – deoxycorticosterone by rat adrenal tissue: zone specificity and effect of sodium and potassium restriction. J. Steroid Biochemistry 13; 253-257.
  10. ^ Tan, S. Y. ; Mulrow, P. J. "Regulation of 18 Hydroxydeoxy-Corticosterone in the Rat. Endocrinology 102: 1113, 1978.
  11. ^ Aguilera, G. ; Lightman, S. L. ; Kiss, A. "Regulation of the Hypothalamic-Pituitary-Adrenal Axis During Water Deprivation. " Endocrinology 132: 241, 1993.
  12. ^ Ahluwalia J Tinker A Clapp LH Duclien MR Abromav AY Pope S Nobles M Segal AW 2004 The large conductance Ca-activated K channel is essential for immunity. Nature 427; 853—858.
  13. ^ Nichols MG Fraser R Hay G Mason P Torsney B 1966 Urine electrolyte response to 18-hydroxy-11-deoxycorticosterone in normal man. Clinical Science Mol. Med. 53; 493-498.
  14. ^ Nichols MG Fraser R Hay G Mason P Torsney B 1977 Urine electrolyte response to 18-hydroxy-11-deoxycorticosterone in normal man. Clin. Sci. Mol. Med. 53(5); 493-498.
  15. ^ Biglieri EG & Lopez JM 1977 Adrenocorticotropin & plasma aldo-sterone concentration and deoxycorticosterone in man. Ann. New York Academy of science 297;361-372.
  16. ^ Williams GH Braley LM Underwood RH 1976 The regulation of plasma 18 hydroxy 11-deoxycorticosterone in man. Journal of Clinical Investigation 58; 221-231.
  17. ^ Moore TJ Braley LM & Williams GH Stimulation of 18-hydroxy-11-deoxycorticosterone secretion by angiotensin II and potassium. Endocrinology 103; 152-155.
  18. ^ Aguilera, G. ; Lightman, S. L. ; Kiss, A. "Regulation of the Hypothalamic-Pituitary-Adrenal Axis During Water Deprivation. " Endocrinology 132: 241, 1993.
  19. ^ Melby JC et al 1972 18-hydroxy 11 deoxycorticosterone (18 OH-DOC) secretion in experimental and human hypertension. Recent Progress in Hormone Research. 28; 287-351, on p323.

Dictionary

mineralocorticoid

-noun

  1. (biochemistry, steroids) Any of a group of steroid hormones, characterised by their similarity to aldosterone and their influence on salt and water metabolism.
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