ALDOSTERONUM

From Big Medical Encyclopedia

ALDOSTERONUM (Aldosteron) — an adrenal hormone of the steroid nature with mineralokortikoidny activity. Aldosteronum is allocated from adrenal glands in a crystal form in 1953 by the Anglo-Swiss group of researchers headed by Simpeon and Tate (S. A. Simpson, J. F. Tait). Aldosteronum is derivative corticosterone at which instead of methyl group is in situation 18 aldehydic (4-Pregnen-18-al-11,21-diol-3,20-dion). In solution Aldosteronum passes into 11,18 inner hemiacetal (fig. 1).

Fig. 1. Constitutional formula of Aldosteronum and its transition to hemiacetal
Fig. 2. The scheme of a biogenesis of Aldosteronum from corticosterone

Biosynthesis of Aldosteronum and its turning into an organism

Aldosteronum is formed in cells of a glomerular zone. The biogenesis of Aldosteronum from corticosterone comes to the end in mitochondrions. Greengard's hypothesis (P. Greengard, 1967) and coauthors provides several stages with participation of enzymes — E and hydrogen acceptors — And (fig. 2). Regulation of secretion of Aldosteronum is closely connected with mechanisms of a water-salt homeostasis and blood circulation. Direct incentives of a biogenesis of Aldosteronum is surplus of potassium ions, a lack of ions of sodium, angiotensin 2 and AKTG. Excess of potassium stimulates a biogenesis of Aldosteronum. Deficit of sodium in an organism is mediated the renin-antpotenzionnoy system (RAS).

Synthesis and allocation of a renin increase first of all as the answer to irritation of the so-called sodium receptors which are localized in a hypothalamus and kidneys. The renal sodium receptor (macula densa) is in initial department of a distal portion of nephron. As the second incentive for increase in secretion of a renin serves the irritation of receptors of the bringing arteriole of a kidney. It arises owing to reduction of volume of blood and a renal blood-groove at blood loss and decrease in minute volume of blood at heart failure. Compensation of these disturbances is connected with reduction of volume of a vascular bed that serves as a signal for system receptors of a kidney; for a renin-angiotenznonnoy of system catecholamines can be a mediator of an incentive. Deficit of sodium works similar to blood loss. At the level of an adrenal gland deficit of ions of sodium causes unique effect, stimulating a biogenesis on the site of transformation of corticosterone into Aldosteronum. This transformation of steroids depends on existence of calcium ions and can be inhibited by means of 18-OH-corticosterone. Angiotensin 2 strengthens education of endogenous predecessors of early stages of a biogenesis of Aldosteronum.

Preferential stimulation of products of Aldosteronum, perhaps, depends on selective reception of angiotensin 2 cells of a glomerular zone of an adrenal gland. The stimulating effect of angiotensin 2 is exponentiated by combined action cyclic Z1,51-adenozinmonofosfata, surplus of potassium ions and a lack of sodium.

Blockade of a genetic transcription in cells of bark of an adrenal gland Actinomycinum of D suppresses a promoting effect of angiotensin 2 on products of Aldosteronum. AKTG does not define regulation of secretion of Aldosteronum in physiological conditions. Supporting a biogenesis of corticosteroids in a glomerular zone, AKTG increases its sensitivity to regulatory incentives. Unlike others corticosteroids (see), Aldosteronum is not capable to make the immediate braking effect on a biogenesis on the mechanism of retroinhibition an end product. Feed-backs in regulation of secretion of Aldosteronum become isolated on a renin-angiotenzionnoy to system.

Aldosteronum reduces secretion of a renin a kidney in two ways: causes oppression of the receptor macula densa function and brakes a barorecrptor incentive from the bringing arterioles by means of increase in volume of plasma. The nature of response of adrenal glands to regulatory incentives depends considerably on their reactivity. In the conditions of activation a renin-angiotenzionnoy of system and adrenocorticotropic function of a hypophysis adrenal glands are capable to answer effect of angiotensin-2 and AKTG with the generalized reaction which is expressed in increase in products of Aldosteronum and cortisol. Ingibition a renin-angiotenzionnoy of system loading of sodium reduces aldosteronstimuliruyushchy effect of angiotensin-2. Reactivity of adrenal glands in relation to angiotensin 2 and AKTG has the seasonal periodical press.

The period of biological life of Aldosteronum makes 24 — 36 minutes. In a blood plasma of 50 — 68% of Aldosteronum it is connected with proteins. The main metabolites of Aldosteronum are the tetra-hydroaldosteronum-glucuronide and 18-oxoglucuronide-Aldosteronum called by a kislotnolabilny conjugate. The sulphated Aldosteronum also belongs to the same fraction of conjugates. Metabolism of Aldosteronum is made mainly in a liver (85 — 92%) and in a smaller measure — in kidneys (5 — 10%). Tetragidrokonjyugata are formed only in a liver, and kislotnolabilny — in a liver and kidneys. At the person and a dog the majority of metabolites of Aldosteronum is excreted with urine (80 — 90%), however at rats the most part them is allocated with a stake and only about 25% with urine.

Physiological action of Aldosteronum

the Biological importance of Aldosteronum consists in its extraordinary high ability to regulate exchange of sodium and by that to participate in maintenance of the general ionic homeostasis connected with many vital functions of an organism. Aldosteronum strengthens the return absorption of sodium in kidneys, sialadens and digestive tract. Normal excess of the detained sodium is transferred by Aldosteronum to the related fraction in bones and sinews. Aldosteronum is more effective than cortexone (DOCK) on ability to detain removal of sodium at adrenalectomized animals by 25 — 40 times and by 100 — 200 times — in maintenance of a ratio sodium/potassium in plasma. Glucocorticoid activity of Aldosteronum equals 1/3 cortisones. The quantity of Aldosteronum necessary for preservation of life of adrenalectomized dogs is 10 — 20 times less than amount of cortexone and by 500 times — cortisol. Aldosteronum in comparison with cortisol more recovers arterial pressure after an adrenalectomy. Aldosteronum exponentiates vasopressor effect of catecholamines and has positive inotropic effect on heart. Kardiotonnchesky action of Aldosteronum is most expressed at a hypodynamia of heart that is very characteristic of adaptive influence of corticosteroids. Molecular mechanisms of action of Aldosteronum are implemented preferential by means of genetic induction of synthesis of the enzymatic systems participating in transmembrane transport of ions and mitochondrions and in a cell in general. These are first of all enzymes of glycolysis and interfaced oxidizing fosforilirovanpya and transport (Na + — K + ) the adenozintrifosfataza providing active removal of sodium from a cell. Perhaps, the inducing action of Aldosteronum extends as well to permeazopodobny enzyme owing to what the diffusion flow of sodium in a cell can increase.

For quantitative assessment of Aldosteronum in peripheral blood several modifications of a method of a double isotope tag are used [Kliman, Peterson (V. of Kliman, R. Peterson), 1960]. The essence of a method comes down to process of transformation of Aldosteronum in aldosteron-diatsetat- 3 H in reaction of acetylation with 3 H-acetic anhydride. The radio immune method of definition of Aldosteronum in plasma of peripheral blood [F. Bayard et al., 1970] is based on measurement of competitive interaction of Aldosteronum of ispytuyemy plasma and the marked standard of hormone with antibodies to Aldosteronum. Antibodies are developed after introduction to rabbits of Aldosteronum covalently connected with a rabbit seralbumin.

For definition of Aldosteronum in the blood flowing from adrenal glands, or conjugates of Aldosteronum in urine various options of paper and thin-layer chromatography with the subsequent quantitative assessment on reaction with tetrazolovy blue are used.

The quantity of Aldosteronum formed by adrenal glands of healthy people is not enough in comparison with other corticosteroids — only 75 — 300 mkg in 24 hours. At the person at rest at horizontal position of a body secretion of Aldosteronum equals 24 ng / mines, and concentration in plasma of peripheral blood — 2 — 17 ng %; daily excretion of a tetra-hydroaldosteronum-glucuronide normal equals 15 — 80 mkg, kislotnolabilny conjugates — 3 — 16 mkg and free Aldosteronum — 0,05 — 0,30 mkg. Secretion of Aldosteronum has accurately expressed day-night rhythm with a maximum in the afternoon if the person passes into vertical position in the morning. As a mediator of postural regulation of secretion of Aldosteronum serves the renin-angiotenzionnaya system. Secretion of Aldosteronum increases at pregnancy, small content of sodium or excess of potassium in food, at blood loss, heart failure, a renal hypertension, cirrhosis, a gidropeksichesky syndrome, etc. (see. Gidropeksichesky syndrome , Giperaldosteronizm ).

Drugs with mineralokortikoidny activity can be applied in clinic with the therapeutic purpose at an addisonovy disease, acute adrenal insufficiency, orthostatic circulator frustration, shock, blood loss and a toxaemia with the phenomena of a hypodynamia of heart (see. Cortexone ). Inhibitors of Aldosteronum are Spironolactonums (Aldactonum, veroshpiron and others).

See also Adrenal glands .



Bibliography: Aldosteronum and adaptation to changes of the water-salt mode, under the editorship of M. G. Kolpakov, L., 1968; Mashkovsky M. D. Pharmaceuticals, p.1, page 392, M., 1972; Sergeyev P. V., Seyfulla R. D. and May A. I. Molecular aspects of effect of steroid hormones, M., 1971, bibliogr.; Steroid hormones, under the editorship of N. A. Yudayev, M., 1969; Functions of the adrenal cortex, ed. by K. W. Me Kerns, v. 1, N. Y., 1967; Glaz E. Vecsei P. Aldosterone, N. Y., 1971, bibliogr.


M. G. Kolpakov.

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