New Mechanisms to Control Aldosterone Synthesis

Abstract

Arterial hypertension is a frequent and leading cardiovascular risk factor, and primary aldosteronism is a well-recognized cause of secondary hypertension. Aldosterone is the basic regulator of extracellular fluid volume and electrolyte balance. Alterations in plasma aldosterone levels significantly contribute to the development and the severity of hypertension. Adrenal steroidogenesis is controlled by two major feedback loops: the hypothalamic–pituitary–adrenal axis, which regulates cortisol synthesis, and the renin–angiotensin–aldosterone system, which directs aldosterone production. In addition to angiotensin, potassium, and corticotropin–which belong to the classic stimulators of aldosterone–neuropeptides, catecholamines, and prostaglandins are also known to stimulate aldosterone synthesis. Recently, several new mechanisms have been characterized that control the release of aldosterone by adrenocortical cells, among them endothelial cell–derived factors and adipokines. Further identification and characterization of these factors may help in the development of novel therapies for the treatment of arterial hypertension, various metabolic diseases, and other disorders.

Key words

aldosterone - renin - angiotensin - adrenal - Conn's syndrome - endothelium - obesity

References

• 1 Conn JW. Presidential address. Part I. Painting background. Part II. Primary aldosteronism, a new clinical syndrome.  J Lab Clin Med. 1955;  45 3-17
• 2 Gross F. Renin und Hypertensin, physiologische oder pathologisehe Wirkstoffe?.  Klin Wschr. 1958;  36 693-706
• 3 Aptel HV, Johnson EIM, Valloton MB, Rossier MF, Capponi AM. Demonstration of an angiotensin II-induced negative feedback effect on aldosterone synthesis in isolated rat adrenal glomerulosa cells.  Mol Cell Endocrinol. 1996;  119 105-111
• 4 Vinson GP, Ho MM, Puddefoot JR, Teja R, Barker S, Kapas S, Hinson JP. The relationship between the adrenal tissue renin-angiotensin system, internalization of the type I angiotensin II receptor (AT1) and angiotensin II function in the rat adrenal zona glomerulosa cell.  Adv Exp Med Biol. 1995;  377 319-329
• 5 Hilbers U, Peters J, Bornstein SR, Correa FM, Jöhren O, Saavedra JM, Ehrhart-Bornstein M. Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells.  Hypertension. 1999;  33 1025-1030
• 6 Hinson JP, Kapas S. The role of endothelial cell products in the regulation of adrenocortical function: actions of endothelin, nitric oxide, adrenomedullin and PAMP.  Horm Metab Res. 1998;  30 334-340
• 7 Brown JJ, Davies DL, Lever AF. Variations in plasma renin concentration in several physiological and pathological states.  Can Med Assoc J. 1964;  90 201-206
• 8 Gaillard RC, Riondel AM, Farrod-Coune CA, Valloton MB, Muller AF. Aldosterone escape to chronic ACTH administration in man.  Acta Endocrinol. 1983;  103 116-124
• 9 Biglieri EG, Herron MA, Brust N. 17-Hydroxylation deficiency in man.  J Clin Invest. 1966;  45 1946-1954
• 10 Abayasekara DR, Vazir H, Whitehouse BJ, Price GM, Hinson JP, Vinson GP. Studies on the mechanisms of ACTH-induced inhibition of aldosterone biosynthesis in the rat adrenal cortex.  J Endocrinol. 1989;  122 625-632
• 11 Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone.  Can Med Assoc J. 1966;  95 1109-1119
• 12 Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM. A chimaeric 11β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.  Nature. 1992;  355 262-265
• 13 Yoshida A, Nishikawa T, Yamura Y, Yoshida S. ACTH-induced inhibition of the action of angitensin II in bovine zona glomerulosa cells.  J Biol Chem. 1991;  266 4288-4294
• 14 Vinson GP, Pudney JA, Whitehouse BJ. The mammalian adrenal circulation and the relationship between adrenal blood flow and steroidogenesis.  Endocrinology. 1985;  105 285-294
• 15 Thomas M, Keramidas M, Monchaux E, Feige JJ. Role of adrenocorticotropic hormone in the development and maintenance of adrenal cortical vasculature.  Microsc Res Tech. 2003;  61 247-251
• 16 Dobbie JW, Symington T. The human adrenal gland with special reference to the vasculature.  J Endocrinol. 1991;  34 479-489
• 17 Bassett JR, West SH. Vascularization of the adrenal cortex: its possible involvement in the regulation of steroid hormone release.  Microsc Res Tech. 1997;  36 546-557
• 18 Miller WL, Redfield MM, Burnett Jr JC. Integrated cardiac, renal, and endocrine actions of endothelin.  J Clin Invest. 1989;  83 317-320
• 19 Hinson JP, Kapas S, Teja R, Vinson GP. Effect of the endothelins on aldosterone secretion by rat zona glomerulosa cells in vitro.  J Steroid Biochem Mol Biol. 1991;  40 43743-43749
• 20 Nussdorfer GG, Rossi GP, Belloni AS. The role of endothelins in the paracrine control of the secretion and growth of the adrenal cortex.  Int Rev Cytology. 1997;  171 267-308
• 21 Mazzocchi G, Rossi GP, Rebuffat P, Malendowicz LK, Markowska A, Nussdorfer GG. Endothelin-1 stimulates deoxyribonucleic acid synthesis and cell proliferation in rat adrenal zona glomerulosa, acting through an endothelin A receptor coupled with protein kinase C-and tyrosine kinase-dependent signaling pathways.  Endocrinology. 1997;  138 2333-2338
• 22 Rossi GP, Belloni AS, Nussdorfer GG, Pessina AC. Endothelin-1 and the adrenal gland.  J Cardiovasc Pharmacol. 2000;  35 S17-S20
• 23 Korth P, Bohle RM, Corvol P, Pine F. Cellular distribution of endothelin-converting enzyme-1 in human tissues.  J Histochem Cytochem. 1999;  47 447-461
• 24 Mohn CE, Fernandez-Solari J, DeLaurentis A, Prestifilippo JP, Cal C de la, Funk R, Bornstein SR, MacCann SM, Rettori V. The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E₂.  Proc Natl Acad Sci USA. 2005;  102 6213-6218
• 25 Jöhren O, Brüggemann N, Dominiak P. Orexins (hypocretins) and adrenal function.  Horm Metab Res. 2004;  36 370-375
• 26 Rosolowsky LJ, Campbell WB. Endothelial cells stimulate aldosterone release from bovine adrenal glomerulosa cells.  Am J Physiol (Endocrinol Metab 29). 1994;  266 E107-E117
• 27 Rosolowsky LJ, Hanke CJ, Campbell WB. Adrenal capillary endothelial cells stimulate aldosterone release through a protein that is distinct from endothelin.  Endocrinology. 1999;  140 4411-4418
• 28 Ansurudeen I, Kopprasch S, Ehrhart-Bornstein M, Willenberg HS, Funk RHW, Krug AW, Bornstein SR. Vascular-adrenal niche – endothelial cell-mediated sensitization of human adrenocortical cells to angiotensin II.  Horm Metab Res. 2006;  38 476-480
• 29 Ansurudeen I, Kopprasch S, Ehrhart-Bornstein M, Bornstein SR, Willenberg HS. Endothelial cell-mediated regulation of aldosterone release from human adrenocortical cells.  Mol Cell Endocrinol. 2007;  265/266 150-156
• 30 Vander AJ. Effect of catecholamines and the renal nerves on renin secretion in anesthetized dogs.  Am J Physiol. 1965;  209 659-662
• 31 Bornstein SR, Ehrhart-Bornstein M, Usadel H, Bockmann M, Scherbaum WA. Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland.  Cell Tissue Res. 1991;  265 1-9
• 32 Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP. Intraadrenal interactions in the regulation of adrenocortical steroidogenesis.  Endocr Rev. 1998;  19 101-143
• 33 Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA, Pfeiffer EF, Holst JJ. Effects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner.  Endocrinology. 1990;  127 900-906
• 34 Ehrhart-Bornstein M, Bornstein SR, Trzeclak WH, Usadel H, Guse-Behling H, Waterman MR, Scherbaum WA. Adrenaline stimulates cholesterol side-chain cleavage cytochrome P450 mRNA accumulation in bovine adrenocortical cells.  J Endocrinol. 1991;  131 ((2)) R5-R8
• 35 Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lubke C, Ehrhart-Bornstein M. Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells.  Endocrinology. 1998;  139 772-780
• 36 Bornstein SR, Tian H, Haidan A, Bottner A, Hiroi N, Eisenhofer G, MacCann SM, Chrousos GP, Roffler-Tarlov S. Deletion of tyrosine hydroxylase gene reveals functional interdependence of adrenocortical and chromaffin cell system in vivo.  Proc Natl Acad Sci USA. 2000;  97 14742-14747
• 37 Szalay KS, Orso E, Juranyi Z, Vinson GP, Vizi ES. Local nonsynaptic modulation of aldosterone production by catecholamines and ATP in rat: implications for a direct neuronal fine tuning.  Horm Metab Res. 1998;  30 323-328
• 38 Willenberg HS, Feldkamp J, Lehmann R, Schott M, Goretzki PE, Scherbaum WA. A case of catecholamine-excess and Cushing's syndrome due to a corticotropin-secreting paraganglioma.  Ann NY Acad Sci. 2006;  1073 52-58
• 39 Müller J, Ziegler WH. Stimulation of aldosterone biosynthesis in vitro by serotonin.  Acta Endocr. 1968;  59 23
• 40 Lefebvre H, Compagnon P, Contesse V, Delarue C, Thuillez C, Vaudry H, Kuhn JM. Production and metabolism of serotonin (5-HT) by the human adrenal cortex: paracrine stimulation of aldosterone secretion by 5-HT.  J Clin Endocrinol Metab. 2001;  86 5001-5007
• 41 Schinner S, Bornstein SR. Cortical-chromaffin cell interactions in the adrenal cortex.  Endocr Pathol. 2005;  16 91-98
• 42 O’Connell NA, Kumar A, Chatzipanteli K, Mohan A, Agarwal RK, Head C, Bornstein SR, Abou-Samra AB, Gwosdow AR. Interleukin-1 regulates corticosterone secretion from the rat adrenal gland through a catecholamine-dependent and prostaglandin E2-independent mechanism.  Endocrinology. 1994;  135 460-467
• 43 Gwosdow AR, O’Connell NA, Spencer JA, Kumar MS, Agarwal RK, Bode HH, Abou-Samra AB. Interleukin-1-induced corticosterone release occurs by an adrenergic mechanism from rat adrenal gland.  Am J Physiol. 1992;  263 E461-E466
• 44 Willenberg HS, Stratakis CA, Marx C, Ehrhart-Bornstein M, Chrousos GP, Bornstein SR. Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing Cushing's syndrome.  N Engl J Med. 1998;  339 27-31
• 45 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue – an update.  Horm Metab Res. 2007;  39 314-321
• 46 Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans.  J Clin Endocrinol Metab. 1993;  77 1690-1694
• 47 Gonzalez-Hernandez JA, Bornstein SR, Ehrhart-Bornstein M, Spath-Schwalbe E, Jirikowski G, Scherbaum WA. Interleukin-6 messenger ribonucleic acid expression in human adrenal gland in vivo: new clue to a paracrine or autocrine regulation of adrenal function.  J Clin Endocrinol Metab. 1994;  79 1492-1497
• 48 Päth G, Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA. Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis.  J Clin Endocrinol Metab. 1997;  82 2343-2349
• 49 Willenberg HS, Path G, Vogeli TA, Scherbaum WA, Bornstein SR. Role of interleukin-6 in stress response in normal and tumorous adrenal cells and during chronic inflammation.  Ann NY Acad Sci. 2002;  966 304-314
• 50 Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients.  N Engl J Med. 1981;  304 930-933
• 51 Rocchini AP, Katch VL, Grekin R, Moorehead C, Anderson J. Role for aldosterone in blood pressure regulation of obese adolescents.  Am J Cardiol. 1986;  57 613-618
• 52 Licata G, Scaglione R, Ganguzza A, Corrao S, Donatelli M, Parrinello G, Dichiara MA, Merlino G, Cecala MG. Central obesity and hypertension. Relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects.  Am J Hypertens. 1994;  7 314-320
• 53 Egan BM, Stepniakowski K, Goodfriend TL. Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering.  Am J Hypertens. 1994;  7 886-893
• 54 Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women.  Obes Res. 1999;  7 355-362
• 55 El-Gharbawy AH, Nadig VS, Kotchen JM, Grim CE, Sagar KB, Kaldunski M, Hamet P, Pausova Z, Gaudet D, Gossard F, Kotchen TA. Arterial pressure, left ventricular mass, and aldosterone in essential hypertension.  Hypertension. 2001;  37 845-850
• 56 Harp JB, Henry SA, DiGirolamo M. Dietary weight loss decreases serum angiotensin-converting enzyme activity in obese adults.  Obes Res. 2002;  10 985-990
• 57 Rankinen T, Gagnon J, Perusse L, Rice T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Body fat, resting and exercise blood pressure and the angiotensinogen M235T polymorphism: the heritage family study.  Obes Res. 1999;  7 423-430
• 58 Ho JT, Keogh JB, Bornstein SR, Ehrhart-Bornstein M, Lewis JG, Clifton PM, Torpy DJ. Moderate weight loss reduces renin and aldosterone but does not influence basal or stimulated pituitary-adrenal axis function.  Horm Metab Res. 2007;  39 694-699
• 59 Blanchette S, Marceau P, Biron S, Brochu G, Tchernof A. Circulating progesterone and obesity in men.  Horm Metab Res. 2006;  38 330-335
• 60 Cooper R, MacFarlane-Anderson N, Bennett FI, Wilks R, Puras A, Tewksbury D, Ward R, Forrester T. ACE, angiotensinogen and obesity: a potential pathway leading to hypertension.  J Hum Hypertens. 1997;  11 107-111
• 61 Penesova A, Cizmarova E, Kvetnansky R, Koska J, Sedlakova B, Krizanova O. Insertion/deletion polymorphism on ACE gene is associated with endothelial dysfunction in young patients with hypertension.  Horm Metab Res. 2006;  38 592-597
• 62 Lamounier-Zepter V, Bornstein SR, Ehrhart-Bornstein M. Mechan-isms of obesity-related hypertension.  Horm Metab Res. 2004;  36 376-380
• 63 Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Metabolic syndrome and the endocrine stress system.  Horm Metab Res. 2006;  38 437-441
• 64 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ.  J Clin Endocrinol Metab. 2004;  89 2548-2556
• 65 Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, Barthel A, Hauner H, MacCann SM, Scherbaum WA, Bornstein SR. Human adipocytes secrete mineralocorticoidreleasing factors.  Proc Natl Acad Sci USA. 2003;  100 14211-14216
• 66 Krug AW, Vleugels K, Schinner S, Lamounier-Zepter V, Ziegler CG, Bornstein SR, Ehrhart-Bornstein M. Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II – sensitization in human adrenocortical cells.  Int J Obes. 2007;  31 1605-1616
• 67 Schinner S, Willenberg HS, Krause D, Schott M, Lamounier-Zepter V, Krug AW, Ehrhart-Bornstein M, Bornstein SR, Scherbaum WA. Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt signaling pathway.  Int J Obes. 2007;  31 864-870
• 68 Chen M, Hornsby PJ. Adenovirus-delivered DKK3/WNT4 and steroidogenesis in primary cultures of adrenocortical cells.  Horm Metab Res. 2006;  38 549-555
• 69 Tadjine M, Lampron A, Ouadi L, Bourdeau I. Frequent mutations of β-catenin gene in sporadic secreting adrenocortical adenomas.  Clin Endocrinol. 2008;  68 264-270
• 70 Lamounier-Zepter V, Rotthoff T, Ansurudeen I, Kopprasch S, Scherbaum WA, Ehrhart-Bornstein M, Bornstein SR. Increased aldosterone/renin quotient in obese hypertensive women: a novel role for low-density lipoproteins?.  Horm Metab Res. 2006;  38 471-475
• 71 Payet MD, Goodfriend TL, Bilodeau L, Mackendale C, Chouinard L, Gallo-Payet N. An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells.  Am J Physiol Endocrinol Metab. 2006;  291 E1160-E1167
• 72 Ueberberg B, Tourne H, Redman A, Walz MK, Schmid KW, Mann K, Petersenn S. Differential expression of the human somatostatin receptor subtypes sst1 to sst5 in various adrenal tumors and normal adrenal gland.  Horm Metab Res. 2005;  37 722-728
• 73 Chang HW, Chu TS, Huang HY, Chueh SC, Wu VC, Chen YM, Hsieh BS, Wu KD. Down-regulation of D2 dopamine receptor and increased protein kinase Cmu phosphorylation in aldosterone-producing adenoma play roles in aldosterone overproduction.  J Clin Endocrinol Metab. 2007;  92 1863-1870
• 74 Boschmann M, Kreuzberg U, Engeli S, Adams F, Franke G, Klaua S, Scholze J, Weidinger G, Luft FC, Sharma AM, Jordan J. The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.  Horm Metab Res. 2006;  38 323-329
• 75 Schjoedt KJ, Jacobsen P, Rossing K, Boomsma F, Parving HH. Dual blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy: the role of aldosterone.  Horm Metab Res. 2005;  37S1 4-8
• 76 Lacroix A, Ndiaye N, Tremblay J, Hamet P. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.  Endocr Rev. 2001;  22 75-110
• 77 Saner-Amigh K, Mayhew BA, Mantero F, Schiavi F, White PC, Rao CV, Rainey WE. Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas.  J Clin Endocrinol Metab. 2006;  91 1136-1142
• 78 Perraudin V, Delarue C, Lefebvre H, Do Rego JL, Vaudry H, Kuhn JM. Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies.  J Clin Endocrinol Metab. 2006;  91 1566-1572
• 79 Bornstein SR, Schuppenies A, Wong ML, Licinio J. Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions.  Mol Psychiatry. 2006;  11 892-902
• 80 Schwarz PEH, Schwarz J, Schuppenies A, Bornstein SR, Schulze J. Development of a diabetes prevention management program for clinical practice.  Public Health Rep. 2007;  122 258-263
• 81 Schwarz PEH, Schwarz J, Bornstein SR, Schulze J. Diabetes preven-tion: from physiology to implementation.  Horm Metab Res. 2006;  38 460-464
• 82 Schwarz PEH, Peltonen M. Prevention of type 2 diabetes – lessons we have learned for implementation.  Horm Metab Res. 2007;  39 636-641
• 83 Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, Appel LJ, Whelton PK. Long term effects of dietary sodium reduc-tion on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP).  Br Med J. 2007;  334 885-893

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