Mineralocorticoids

From Proteopedia

Mineralocorticoids are a class of corticosteroids. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mineralocorticoid is aldosterone. Mineralocorticoid receptor (MR) in epithelial cells is activated by the mineralocorticoid hormone aldosterone promoting renal sodium retention and potassium excretion. It is nuclear receptor. In non epithelial cells MR is activated by cortisol[1]. MR is exposed to many steroids including cortisol, cortisone and progesterone, however, aldosterone and deoxycorticosterone are its physiological ligands. MR mutations are the principal cause of renal pseudohypoaldosteronism[2]. MR mutation S810L causes early-onset hypertension[3]. Inhibition of cardia MR prevents doxorubicin-induced cardiotoxicity[4]. MR is an important proadipogenic transcription factor that may mediate aldosterone and glucocorticoid effects on adipose tissue development and hence on obesity and development of metabolic syndrome[5]. The MR ligand aldosterone binds in a fully enclosed pocket, contacting residues with six α-helices and a β-turn (Alpha Helices, Beta Strands , Loops ,Turns). It forms hydrogen bonds with 4 MR residues[6]. Whole binding site. Water molecules are shown as red spheres. Angiotensin-Converting Enzyme, Renin-Angiotensin-Aldosterone System. Corticosteroid-binding globulin Hydroxysteroid dehydrogenase

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See also:

• Steroid Hormones and their receptors

References

1. ↑ Frey FJ, Odermatt A, Frey BM. Glucocorticoid-mediated mineralocorticoid receptor activation and hypertension. Curr Opin Nephrol Hypertens. 2004 Jul;13(4):451-8. PMID:15199296
2. ↑ Pujo L, Fagart J, Gary F, Papadimitriou DT, Claes A, Jeunemaitre X, Zennaro MC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40. PMID:16972228 doi:10.1002/humu.20371
3. ↑ Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23. PMID:10884226
4. ↑ Lother A, Bergemann S, Kowalski J, Huck M, Gilsbach R, Bode C, Hein L. Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates doxorubicin-induced cardiotoxicity. Cardiovasc Res. 2018 Feb 1;114(2):282-290. doi: 10.1093/cvr/cvx078. PMID:28430882 doi:http://dx.doi.org/10.1093/cvr/cvx078
5. ↑ Caprio M, Feve B, Claes A, Viengchareun S, Lombes M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J. 2007 Jul;21(9):2185-94. doi: 10.1096/fj.06-7970com. Epub 2007 Mar 23. PMID:17384139 doi:http://dx.doi.org/10.1096/fj.06-7970com
6. ↑ Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794 doi:http://dx.doi.org/10.1074/jbc.M504098200