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DOI: 10.1055/a-1157-0511
The Effect of Extracellular Calcium Metabolism on Aldosterone Biosynthesis in Physiological and Pathological Status
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Abstract
Primary aldosteronism (PA) was reported to frequently harbor not only cardiovascular diseases but also some metabolic disorders including secondary calcium metabolic diseases. Recently, the potential association between aldosterone producing cells and systemic calcium metabolism has been proposed. For instance, PA is frequently associated with hypercalciuria or hypocalcemia, which subsequently stimulates parathyroid hormone (PTH) secretion. This altered calcium metabolism in PA patients could frequently result in secondary osteoporosis and fracture in some patients. On the other hand, extracellular calcium itself directly acts on adrenal cortex and has been also proposed as an independent regulator of aldosterone biosynthesis in human adrenals. However, it is also true that both PTH and vitamin D pathways stimulate endocrine functions of adrenal cortical adenomas to co-secret both aldosterone and cortisol. Therefore, it has become pivotal to explore the potential crosstalk between aldosterone and systemic calcium metabolism. We herein reviewed recent advances in these fields.
Publication History
Received: 30 November 2019
Accepted: 30 March 2020
Article published online:
13 May 2020
© Georg Thieme Verlag KG
Stuttgart · New York
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References
- 1 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300
- 2 Funder JW. The genetics of primary aldosteronism: Chapter two. Hypertension 2012; 59: 537-538
- 3 Williams JS, Williams GH, Raji A. et al. Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. J Hum Hypertens 2006; 20: 129-136
- 4 Byrd JB, Turcu AF, Auchus RJ. Primary aldosteronism. Circulation 2018; 138: 823-835
- 5 Altieri B, Muscogiuri G, Paschou SA. et al. Adrenocortical incidentalomas and bone: From molecular insights to clinical perspectives. Endocrine 2018; 62: 506-516
- 6 Elliott WJ. Systemic hypertension. Curr Probl Cardiol 2007; 32: 201-259
- 7 Quereda C, Orte L, Sabater J. et al. Urinary calcium excretion in treated and untreated essential hypertension. J Am Soc Nephrol 1996; 7: 1058-1065
- 8 McCarron DA, Pingree PA, Rubin RJ. et al. Enhanced parathyroid function in essential hypertension: A homeostatic response to a urinary calcium leak. Hypertension 1980; 2: 162-168
- 9 Resnick LM, Muller FB, Laragh JH. Calcium-regulating hormones in essential hypertension. Relation to plasma renin activity and sodium metabolism. Ann Intern Med 1986; 105: 649-654
- 10 Hazari MA, Arifuddin MS, Muzzakar S. et al. Serum calcium level in hypertension. N Am J Med Sci 2012; 4: 569-572
- 11 Gennari C, Nami R, Bianchini C. et al. Renal excretion of calcium in human hypertension. Am J Nephrol. 1986; 06 (Suppl. 01) 124-127
- 12 Pointer MA, Eley S, Anderson L. et al. Differential effect of renal cortical and medullary interstitial fluid calcium on blood pressure regulation in salt-sensitive hypertension. Am J Hypertens 2015; 28: 1049-1055
- 13 Hamet P, Daignault-Gelinas M, Lambert J. et al. Epidemiological evidence of an interaction between calcium and sodium intake impacting on blood pressure. A Montreal study. Am J Hypertens 1992; 5: 378-385
- 14 Salcuni AS, Palmieri S, Carnevale V. et al. Bone involvement in aldosteronism. J Bone Miner Res 2012; 27: 2217-2222
- 15 Maniero C, Fassina A, Seccia TM. et al. Mild hyperparathyroidism: A novel surgically correctable feature of primary aldosteronism. J Hypertens 2012; 30: 390-395
- 16 Tomaschitz A, Ritz E, Pieske B. et al. Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease. Metabolism 2014; 63: 20-31
- 17 Petramala L, Zinnamosca L, Settevendemmie A. et al. Bone and mineral metabolism in patients with primary aldosteronism. Int J Endocrinol. 2014 836529.
- 18 Salcuni AS, Carnevale V, Battista C. et al. Primary aldosteronism as a cause of secondary osteoporosis. Eur J Endocrinol 2017; 177: 431-437
- 19 Hu C, Rusin CG, Tan Z. et al. Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators. J Clin Invest 2012; 122: 2046-2053
- 20 Nakamura Y, Yamazaki Y, Tezuka Y. et al. Expression of CYP11B2 in aldosterone-producing adrenocortical adenoma: Regulatory mechanisms and clinical significance. Tohoku J Exp Med 2016; 240: 183-190
- 21 Yamazaki Y, Nakamura Y, Omata K. et al. Histopathological classification of cross-sectional image-negative hyperaldosteronism. J Clin Endocrinol Metab 2017; 102: 1182-1192
- 22 Omata K, Satoh F, Morimoto R. et al. Cellular and genetic causes of idiopathic hyperaldosteronism. hypertension 2018; 72: 874-880
- 23 Ceccoli L, Ronconi V, Giovannini L. et al. Bone health and aldosterone excess. Osteoporos Int 2013; 24: 2801-2807
- 24 Rossi GP, Ragazzo F, Seccia TM. et al. Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma. Hypertension 2012; 60: 431-436
- 25 Hattangady NG, Olala LO, Bollag WB. et al. Acute and chronic regulation of aldosterone production. Mol Cell Endocrinol 2012; 350: 151-162
- 26 Li YC, Qiao G, Uskokovic M. et al. Vitamin D: A negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol 2004; 89–90: 387-392
- 27 Lundqvist J, Wikvall K, Norlin M. Vitamin D-mediated regulation of CYP21A2 transcription - A novel mechanism for vitamin D action. Biochim Biophys Acta 2012; 1820: 1553-1559
- 28 Bi C, Li B, Du L. et al. Vitamin D receptor, an important transcription factor associated with aldosterone-producing adenoma. PLoS One 2013; 8: e82309
- 29 Zhang B, Umbach AT, Chen H. et al. Up-regulation of FGF23 release by aldosterone. Biochem Biophys Res Commun 2016; 470: 384-390
- 30 Mhatre KN, Wakula P, Klein O. et al. Crosstalk between FGF23- and angiotensin II-mediated Ca(2+) signaling in pathological cardiac hypertrophy. Cell Mol Life Sci 2018; 75: 4403-4416
- 31 Gao X, Yamazaki Y, Tezuka Y. et al. The crosstalk between aldosterone and calcium metabolism in primary aldosteronism: A possible calcium metabolism-associated aberrant "neoplastic" steroidogenesis in adrenals. J Steroid Biochem Mol Biol 2019; 193: 105434
- 32 Schiebinger RJ, Braley LM, Menachery A. et al. Calcium, a “third messenger” of cAMP-stimulated adrenal steroid secretion. Am J Physiol 1985; 248: E89-E94
- 33 King JS, Jackson R, Ashe B. Relation of Sodium intake to urinary calcium excretion. Invest Urol 1964; 1: 555-560
- 34 Beierwaltes WH. The role of calcium in the regulation of renin secretion. Am J Physiol Renal Physiol 2010; 298: F1-F11
- 35 Riccardi D, Valenti G. Localization and function of the renal calcium-sensing receptor. Nat Rev Nephrol 2016; 12: 414-425
- 36 Hannan FM, Kallay E, Chang W. et al. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat Rev Endocrinol 2018; 15: 33-51
- 37 Bollag WB. Regulation of aldosterone synthesis and secretion. Compr Physiol 2014; 4: 1017-1055
- 38 Yingst DR, Davis J, Schiebinger R. Effects of extracellular calcium and potassium on the sodium pump of rat adrenal glomerulosa cells. Am J Physiol Cell Physiol 2001; 280: C119-C125
- 39 Chin D, Means AR. Calmodulin: A prototypical calcium sensor. Trends Cell Biol 2000; 10: 322-328
- 40 Means AR. Regulatory cascades involving calmodulin-dependent protein kinases. Mol Endocrinol 2000; 14: 4-13
- 41 Nanba K, Chen A, Nishimoto K. et al. Role of Ca(2+)/calmodulin-dependent protein kinase kinase in adrenal aldosterone production. Endocrinology 2015; 156: 1750-1756
- 42 Pezzi V, Clark BJ, Ando S. et al. Role of calmodulin-dependent protein kinase II in the acute stimulation of aldosterone production. J Steroid Biochem Mol Biol 1996; 58: 417-424
- 43 Condon JC, Pezzi V, Drummond BM. et al. Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology 2002; 143: 3651-3657
- 44 Fern RJ, Hahm MS, Lu HK. et al. Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling. Am J Physiol 1995; 269: F751-F760
- 45 Olgaard K, Lewin E, Bro S. et al. Enhancement of the stimulatory effect of calcium on aldosterone secretion by parathyroid hormone. Miner Electrolyte Metab 1994; 20: 309-314
- 46 Isales CM, Barrett PQ, Brines M. et al. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology 1991; 129: 489-495
- 47 Mazzocchi G, Aragona F, Malendowicz LK. et al. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metab 2001; 280: E209-E213
- 48 Maniero C, Fassina A, Guzzardo V. et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension 2011; 58: 341-346
- 49 El Ghorayeb N, Bourdeau I, Lacroix A. Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism. Front Endocrinol (Lausanne) 2016; 7: 72
- 50 Rainey WE. Adrenal zonation: Clues from 11beta-hydroxylase and aldosterone synthase. Mol Cell Endocrinol 1999; 151: 151-160
- 51 Johannessen M, Moens U. Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. Front Biosci 2007; 12: 1814-1832
- 52 Spat A, Hunyady L, Szanda G. Signaling interactions in the adrenal cortex. Front Endocrinol (Lausanne) 2016; 7: 17
- 53 Wang R, Wu LY, Karpinski E. et al. The effects of parathyroid hormone on L-type voltage-dependent calcium channel currents in vascular smooth muscle cells and ventricular myocytes are mediated by a cyclic AMP dependent mechanism. FEBS Lett 1991; 282: 331-334
- 54 Prideaux M, Dallas SL, Zhao N. et al. Parathyroid hormone induces bone cell motility and loss of mature osteocyte phenotype through l-calcium channel dependent and independent mechanisms. PLoS One 2015; 10: e0125731
- 55 Li J, Zhao L, Ferries IK. et al. Skeletal phenotype of mice with a null mutation in Cav 1.3 L-type calcium channel. J Musculoskelet Neuronal Interact 2010; 10: 180-187
- 56 Ismail NA, Kamaruddin NA, Azhar Shah S. et al. The effect of vitamin D treatment on clinical and biochemical outcomes of primary aldosteronism. Clin Endocrinol (Oxf); 2020 DOI: 10.1111/cen.14177 [Epub ahead of print].
- 57 Romero DG, Rilli S, Plonczynski MW. et al. Adrenal transcription regulatory genes modulated by angiotensin II and their role in steroidogenesis. Physiol Genomics 2007; 30: 26-34
- 58 Brown JM, Williams JS, Luther JM. et al. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension 2014; 63: 273-280
- 59 Fumoto T, Ishii KA, Ito M. et al. Mineralocorticoid receptor function in bone metabolism and its role in glucocorticoid-induced osteopenia. Biochem Biophys Res Commun 2014; 447: 407-412
- 60 Manelli F, Giustina A. Glucocorticoid-induced osteoporosis. Trends Endocrinol Metab 2000; 11: 79-85
- 61 Park SM, Jee J, Joung JY. et al. High dietary sodium intake assessed by 24-hour urine specimen increase urinary calcium excretion and bone resorption marker. J Bone Metab 2014; 21: 189-194
- 62 Kleeman CR, Bohannan J, Bernstein D. et al. Effect of variations in sodium intake on calcium excretion in normal humans. Proc Soc Exp Biol Med 1964; 115: 29-32
- 63 Belden Z, Deiuliis ZA, Dobre M. et al. The Role of the mineralocorticoid receptor in inflammation: focus on kidney and vasculature. Am J Nephrol 2017; 46: 298-314
- 64 Mene P, Punzo G, Pirozzi N. TRP channels as therapeutic targets in kidney disease and hypertension. Curr Top Med Chem 2013; 13: 386-397