Question

List at least two mineral corticoids and describe their general chemical structure, their target cells and general action, and the mechanism of control for mineral corticoids.

Answer 1

The mineralcorticoid is used to describe those actions.The most important mineralcorticoid is aldosterone which,like other mineralocorticoid receptor it involves in the activation of receptor through transcription rates of various genes.the only mineralocorticoid used clinically is fludrocortisone.

Aldosterone:

molecular formula for this C21H28O5,molecular weight 360.4 g/mol.

it is a 11 beta-hydroxy steroid,a 21-hydroxy steroid,18-oxo steroid,20-oxo steroid,a C21-steroid harmone,a steroid aldehyde,3-oxo delta steroid,and primary alpha-hydroxy ketone and mineralocorticoid ,it derives from the hydrine of a pregnane.properties of this molecule is melting point-166.5 C Solubility-51.2 mg/L

Fludrocortisone:

molecular formula for this compound is C21H29FO5 molecular weight 380.4g/mol,9α-fluorocortisol or as 9α-fluoro-11β,17α,21-trihydroxypregn-4-ene-3,20.

Target cells and general actions:In sodium reabsorbing epithelia, it has been well established that aldosterone activates plasma membrane sodium channels. Aldosterone elicits cellular responses in human endothelial cells similar as compared with cells of the renal collecting duct. In kidney, the major target is the principal cell of the distal nephron where systemic sodium deprivation, and hence increase of plasma aldosterone concentration, stimulates amiloride-sensitive electrical currents as measured by patch-clamp techniques.These currents are caused by active sodium channels in apical plasma membrane that are activated by aldosterone either through yet unknown nongenomic mechanisms or through classic genomic mechanisms using intracellular mineralocorticoid receptors.This sequence of events is likely to occur not only in renal target cells but also in cells of the cardiovascular system including endothelial cells. In any case, induction of sodium channels causes cells to electrically depolarize because of increased sodium influx. Although sodium is pumped out of the cell by the Na+/K+ATPase, located in the basolateral membrane, Cl− accumulates in the cell because of electrochemical driving forces set by the altered cell membrane potential. This causes intracellular retention of water and cell swelling.The amiloride response can be explained in a similar way. It is evident that only cells with significant sodium permeability, based on epithelial sodium channel activity, can respond to micromolar amiloride concentrations. Such increased sodium permeability exists in HUVECs after aldosterone treatment. Under these conditions, application of amiloride blocks the apical sodium channels and thus hyperpolarizes the cell membrane.

Fludrocortisone is a synthetic mineralocorticoid used in conjunction with hydrocortisone to replace missing endogenous corticosteroids in patients with adrenal insufficiency. It is functionally similar to aldosterone, the body's primary endogenous mineralocorticoid, and is structurally analogous to cortisol, differing only by a fluorine atom at the 9-position of the steroid structure - this fluorination is thought to be crucial to fludrocortisone's significant mineralocorticoid potency.Fludrocortisone is indicated as partial replacement therapy for primary or secondary adrenocortical insufficiency in Addison's disease. It is also indicated for the treatment of salt-losing androgenital syndrome.

The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure. In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.

Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na+-K+-ATPase on the basolateral side.These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na+-H+ exchanger found in the apical membrane of renal tubule cells.

mechanism of control for mineralocorticoids:

controls intracellular pH in the cardiovascular system, providing protection from the acidification that follows ischemia and is thus a potential intermediate in the translation of MR signaling into vascular inflammation and perivascular fibrosis. Indeed, the specific NHE-1 antagonist cariporide can reverse postischemic changes such as cardiac hypertrophy, arrhythmia, and impaired contractility.modulation of intracellular pH and thereby promotes vascular damage. If the primary effects of circulating aldosterone are on the coronary vasculature or cardiac myocytes, such effects may be via either modulation of gene transcription or sustained activation of nongenomic pathways