Subscribe to RSS
DOI: 10.1055/s-0029-1243602
© Georg Thieme Verlag KG Stuttgart · New York
Aberrant Hormone Receptors in Primary Aldosteronism
Publication History
received 13.10.2009
accepted 23.11.2009
Publication Date:
07 January 2010 (online)

Abstract
The mechanisms involved in the renin-independent regulation of aldosterone secretion in primary aldosteronism are poorly understood. In ACTH-independent Cushing's syndrome, cortisol secretion can be regulated by the aberrant expression of G-protein coupled receptors (GPCRs) in unilateral tumors and bilateral macronodular adrenal hyperplasia. By analogy, some recent studies identified overexpression or function of several GPCR as a potential cause for excess aldosterone production in some aldosteronomas and in bilateral idiopathic hyperaldosteronism. Initial studies have used in vitro techniques, while the clinical aldosterone responses were not assessed. More recently, several receptors have been shown to be expressed in aldosterone-producing adrenal tumors in vitro and to regulate aberrantly renin-independent aldosterone secretion in vivo. The prevalence of aberrant hormone receptors in primary aldosteronism could be elevated, but larger systematic studies are required to establish its true frequency. The identification of aberrant adrenal GPCRs by in vivo functional studies offers the potential for novel pharmacological therapies that either suppress the endogenous ligands or block the receptor with specific antagonists.
Key words
primary aldosteronism - adrenal glands - G-protein coupled receptors - aldosterone
References
- 1
Lacroix A, Baldacchino V, Bourdeau I, Hamet P, Tremblay J.
Cushing's syndrome variants secondary to aberrant hormone receptors.
Trends Endocrinol Metab.
2004;
15
375-382
MissingFormLabel
- 2
Lacroix A, Bourdeau I, Lampron A, Mazzuco TL, Tremblay J, Hamet P.
Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction.
Clin Endocrinol (Oxf).
2009;
E-pub Aug 29
DOI: 10.1111/j.1365-2265.2009.03689.x
MissingFormLabel
- 3
Arnaldi G, Mancini V, Costantini C, Giovagnetti M, Petrelli M, Masini A, Bertagna X, Mantero F.
ACTH receptor mRNA in human adrenocortical tumors: overexpression in aldosteronomas.
Endocr Res.
1998;
24
845-849
MissingFormLabel
- 4
Lampron A, Bourdeau I, Oble S, Godbout A, Schurch W, Arjane P, Hamet P, Lacroix A.
Regulation of aldosterone secretion by several aberrant receptors including for glucose-dependent
insulinotropic peptide in a patient with an aldosteronoma.
J Clin Endocrinol Metab.
2009;
94
750-756
MissingFormLabel
- 5
Zwermann O, Suttmann Y, Bidlingmaier M, Beuschlein F, Reincke M.
Screening for Membrane Hormone Receptor Expression in Primary Aldosteronism.
Eur J Endocrinol.
2009;
160
443-451
MissingFormLabel
- 6
Schubert B, Fassnacht M, Beuschlein F, Zenkert S, Allolio B, Reincke M.
Angiotensin II type 1 receptor and ACTH receptor expression in human adrenocortical
neoplasms.
Clin Endocrinol (Oxf).
2001;
54
627-632
MissingFormLabel
- 7
Lefebvre H, Cartier D, Duparc C, Lihrmann I, Contesse V, Delarue C, Godin M, Fischmeister R, Vaudry H, Kuhn JM.
Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing
adenomas: in vivo and in vitro studies.
J Clin Endocrinol Metab.
2002;
87
1211-1216
MissingFormLabel
- 8
Lacroix A, Tremblay J, Rousseau G, Bouvier M, Hamet P.
Propranolol therapy for ectopic beta-adrenergic receptors in adrenal Cushing's syndrome.
N Engl J Med.
1997;
337
1429-1434
MissingFormLabel
- 9
Willenberg HS, Schinner S, Ansurudeen I.
New mechanisms to control aldosterone synthesis.
Horm Metab Res.
2008;
40
435-441
MissingFormLabel
- 10
Williams GH.
Aldosterone biosynthesis, regulation, and classical mechanism of action.
Heart Fail Rev.
2005;
10
7-13
MissingFormLabel
- 11
Capponi AM.
The control by angiotensin II of cholesterol supply for aldosterone biosynthesis.
Mol Cell Endocrinol.
2004;
217
113-118
MissingFormLabel
- 12
Gupta P, Franco-Saenz R, Mulrow PJ.
Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-,
and potassium-stimulated aldosterone secretion.
Hypertension.
1995;
25
443-448
MissingFormLabel
- 13
Mazzocchi G, Malendowicz LK, Macchi C, Gottardo G, Nussdorfer GG.
Further investigations on the effects of neuropeptide Y on the secretion and growth
of rat adrenal zona glomerulosa.
Neuropeptides.
1996;
30
19-27
MissingFormLabel
- 14
Bornstein SR, Chrousos GP.
Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation
of the adrenal cortex: neural and immune inputs.
J Clin Endocrinol Metab.
1999;
84
1729-1736
MissingFormLabel
- 15
Gallo-Payet N, Grazzini E, Cote M, Chouinard L, Chorvatova A, Bilodeau L, Payet MD, Guillon G.
Role of Ca2+ in the action of adrenocorticotropin in cultured human adrenal glomerulosa
cells.
J Clin Invest.
1996;
98
460-466
MissingFormLabel
- 16
Feige JJ, Keramidas M, Chambaz EM.
Hormonally regulated components of the adrenocortical cell environment and the control
of adrenal cortex homeostasis.
Horm Metab Res.
1998;
30
421-425
MissingFormLabel
- 17
Otis M, Campbell S, Payet MD, Gallo-Payet N.
Expression of extracellular matrix proteins and integrins in rat adrenal gland: importance
for ACTH-associated functions.
J Endocrinol.
2007;
193
331-347
MissingFormLabel
- 18
Missale C, Memo M, Liberini P, Spano P.
Dopamine selectively inhibits angiotensin II-induced aldosterone secretion by interacting
with D-2 receptors.
J Pharmacol Exp Ther.
1988;
246
1137-1143
MissingFormLabel
- 19
Kasprzak A, Rebuffat P, Andreis PG, Mazzocchi G, Nussdorfer GG.
Effects of prolonged cysteamine administration on the rat adrenal cortex: evidence
that endogenous somatostatin is involved in the control of the growth and steroidogenic
capacity of zona glomerulosa.
J Steroid Biochem Mol Biol.
1991;
38
469-473
MissingFormLabel
- 20
Cherradi N, Brandenburger Y, Rossier MF, Vallotton MB, Stocco DM, Capponi AM.
Atrial natriuretic peptide inhibits calcium-induced steroidogenic acute regulatory
protein gene transcription in adrenal glomerulosa cells.
Mol Endocrinol.
1998;
12
962-972
MissingFormLabel
- 21
Gallo-Payet N, Guillon G.
Regulation of adrenocortical function by vasopressin.
Horm Metab Res.
1998;
30
360-367
MissingFormLabel
- 22
Lefebvre H, Gonzalez KN, Contesse V, Delarue C, Vaudry H, Kuhnl JM.
Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride
on aldosterone secretion in healthy volunteers.
Endocr Res.
1998;
24
749-752
MissingFormLabel
- 23
Hinson JP, Kapas S, Orford CD, Vinson GP.
Vasoactive intestinal peptide stimulation of aldosterone secretion by the rat adrenal
cortex may be mediated by the local release of catecholamines.
J Endocrinol.
1992;
133
253-258
MissingFormLabel
- 24
Gross MD, Grekin RJ, Gniadek TC, Villareal JZ.
Suppression of aldosterone by cyproheptadine in idiopathic aldosteronism.
N Engl J Med.
1981;
305
181-185
MissingFormLabel
- 25
Ganguly A, Pratt JH, Weinberger MH, Grim CE, Fineberg NS.
Differing effects of metoclopramide and adrenocorticotropin on plasma aldosterone
levels in glucocorticoid-suppressible hyperaldosteronism and other forms of hyperaldosteronism.
J Clin Endocrinol Metab.
1983;
57
388-392
MissingFormLabel
- 26
Mantero F, Rocco S, Opocher G, Armanini D, Boscaro M, D’Agostino D.
Effect of ketanserin in primary aldosteronism.
J Cardiovasc Pharmacol.
1985;
7
((Suppl 7))
S172-S175
MissingFormLabel
- 27
Lefebvre H, Contesse V, Delarue C, Soubrane C, Legrand A, Kuhn JM, Wolf LM, Vaudry H.
Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from
the human adrenal cortex: in vivo and in vitro studies.
J Clin Endocrinol Metab.
1993;
77
1662-1666
MissingFormLabel
- 28
Lefebvre H, Dhib M, Godin M, Contesse V, Delarue C, Rieu M, Wolf LM, Vaudry H, Kuhn JM.
Effect of the serotonin 5-HT4 receptor agonist cisapride on aldosterone secretion
in corticotropic insufficiency and primary hyperaldosteronism.
Neuroendocrinology.
1997;
66
229-233
MissingFormLabel
- 29
Nomura K, Toraya S, Horiba N, Ujihara M, Aiba M, Demura H.
Plasma aldosterone response to upright posture and angiotensin II infusion in aldosterone-producing
adenoma.
J Clin Endocrinol Metab.
1992;
75
323-327
MissingFormLabel
- 30
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
MissingFormLabel
- 31
Schorr I, Ney RL.
Abnormal hormone responses of an adrenocortical cancer adenyl cyclase.
J Clin Invest.
1971;
50
1295-1300
MissingFormLabel
- 32
Schorr I, Rathnam P, Saxena BB, Ney RL.
Multiple specific hormone receptors in the adenylate cyclase of an adrenocortical
carcinoma.
J Biol Chem.
1971;
246
5806-5811
MissingFormLabel
- 33 Hinshaw HT, Ney RL. Abnormal hormonal control in the neoplastic adrenal cortex. In: Mckerns K W (ed).
Hormones and cancer . New York: Academic press 1974: 309-327MissingFormLabel - 34
Lacroix A, Ndiaye N, Tremblay J, Hamet P.
Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.
Endocr Rev.
2001;
22
75-110
MissingFormLabel
- 35
Mune T, Murase H, Yamakita N, Fukuda T, Murayama M, Miura A, Suwa T, Hanafusa J, Daido H, Morita H, Yasuda K.
Eutopic overexpression of vasopressin v1a receptor in adrenocorticotropin-independent
macronodular adrenal hyperplasia.
J Clin Endocrinol Metab.
2002;
87
5706-5713
MissingFormLabel
- 36
Cartier D, Jegou S, Parmentier F, Lihrmann I, Louiset E, Kuhn JM, Bastard C, Plouin PF, Godin M, Vaudry H, Lefebvre H.
Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing
adenomas.
Eur J Endocrinol.
2005;
153
939-947
MissingFormLabel
- 37
Christopoulos S, Cartier D, Yared Z, Bourdeau I, Lefebvre H, Lacroix A.
Serotonin (5-HT4) Receptor Isoform Characterization in a 5-HT4 agonist-responsive ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH) causing
Primary Hyperaldosteronism and Cyclical Cushing's Syndrome (CS).
The Endocrine Society 87th Meeting, San Diego.
2005;
Abstract P1-634
MissingFormLabel
- 38
Rossi GP, Sticchi D, Giuliani L, Bernante P, Zavattiero S, Pessina AC, Nussdorfer GG.
Adiponectin receptor expression in the human adrenal cortex and aldosterone-producing
adenomas.
Int J Mol Med.
2006;
17
975-980
MissingFormLabel
- 39
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
MissingFormLabel
- 40
Ye P, Mariniello B, Mantero F, Shibata H, Rainey WE.
G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of
hyperaldosteronism.
J Endocrinol.
2007;
195
39-48
MissingFormLabel
- 41
Mariniello B, Sartorato P, Albiger N, Lacobone M, Finco I, Patalano A, Rainey WE, Mantero F.
The role of LH and GnRH receptors (LH-R and GnRH-R) in primary aldosteronism (PA):
clinical and molecular data.
35th Annual Meeting of the International Aldosterone Conference, Washington, DC
2009;
((Abstract))
32-33
MissingFormLabel
- 42
Shenker Y, Gross MD, Grekin RJ.
Central serotonergic stimulation of aldosterone secretion.
J Clin Invest.
1985;
76
1485-1490
MissingFormLabel
- 43
Duparc C, Louiset E, Perraudin V, Gobet F, Meatchi T, Plouin PF, Zennaro MC, Lefebvre H.
Immunohistochemical caracterisation of mast cells in aldosterone-producing adenomas.
35th Annual Meeting of the International Aldosterone Conference, Washington, DC
2009;
((Abstract))
31-32
MissingFormLabel
- 44
Costa MH, Lampron A, Godbout A, Ste-Marie LG, Bourdeau I, Lacroix A.
In vivo screening for aberrant hormone responsiveness in primary aldosteronism.
The Endocrine Society 89th Meeting, Toronto.
2007;
((Abstract))
P1-P163
MissingFormLabel
- 45
Abdallah MA, Lei ZM, Li X, Greenwold N, Nakajima ST, Jauniaux E, Rao Ch V.
Human fetal nongonadal tissues contain human chorionic gonadotropin/luteinizing hormone
receptors.
J Clin Endocrinol Metab.
2004;
89
952-956
MissingFormLabel
- 46
Pabon JE, Li X, Lei ZM, Sanfilippo JS, Yussman MA, Rao CV.
Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal
glands.
J Clin Endocrinol Metab.
1996;
81
2397-2400
MissingFormLabel
- 47
Godbout A, Ste-Marie LG, Larochelle P, Lamarre-Cliche M, Bourdeau I, Lacroix A.
Aberrant regulation of aldosterone and cortisol secretion in patients with clinical
primary aldosteronisme and bilateral macronodular adrenal hyperplasia.
The Endocrine Society 90th Meeting, San Fransisco.
2008;
((Abstract))
P3-P271
MissingFormLabel
- 48
Tanabe A, Naruse M, Arai K, Naruse K, Yoshimoto T, Seki T, Imaki T, Miyazaki H, Zeng ZP, Demura R, Demura H.
Gene expression and roles of angiotensin II type 1 and type 2 receptors in human adrenals.
Horm Metab Res.
1998;
30
490-495
MissingFormLabel
- 49
Jezova M, Armando I, Bregonzio C, Yu ZX, Qian S, Ferrans VJ, Imboden H, Saavedra JM.
Angiotensin II AT(1) and AT(2) receptors contribute to maintain basal adrenomedullary
norepinephrine synthesis and tyrosine hydroxylase transcription.
Endocrinology.
2003;
144
2092-2101
MissingFormLabel
- 50
Sachse R, Shao XJ, Rico A, Finckh U, Rolfs A, Reincke M, Hensen J.
Absence of angiotensin II type 1 receptor gene mutations in human adrenal tumors.
Eur J Endocrinol.
1997;
137
262-266
MissingFormLabel
- 51
Nakamura Y, Son Y, Kohno Y, Shimono D, Kuwamura N, Koshiyama H, Sasano H, Matsuda T.
Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with
possible adrenal hypersensitivity to angiotensin II.
Endocrine.
2001;
15
57-61
MissingFormLabel
- 52
N’Diaye N, Tremblay J, Hamet P, De Herder WW, Lacroix A.
Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies
food-dependent Cushing's syndrome.
J Clin Endocrinol Metab.
1998;
83
2781-2785
MissingFormLabel
- 53
Matsukura S, Kakita T, Sueoka S, Yoshimi H, Hirata Y, Yokota M, Fujita T.
Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors.
Cancer Res.
1980;
40
3768-3771
MissingFormLabel
- 54
Hirata Y, Uchihashi M, Sueoka S, Matsukura S, Fujita T.
Presence of ectopic beta-adrenergic receptors on human adrenocortical cortisol-producing
adenomas.
J Clin Endocrinol Metab.
1981;
53
953-957
MissingFormLabel
- 55
Katz MS, Kelly TM, Dax EM, Pineyro MA, Partilla JS, Gregerman RI.
Ectopic beta-adrenergic receptors coupled to adenylate cyclase in human adrenocortical
carcinomas.
J Clin Endocrinol Metab.
1985;
60
900-909
MissingFormLabel
- 56
Mazzuco TL, Thomas M, Martinie M, Cherradi N, Sturm N, Feige JJ, Chabre O.
Cellular and molecular abnormalities of a macronodular adrenal hyperplasia causing
beta-blocker-sensitive Cushing's syndrome.
Arq Bras Endocrinol Metabol.
2007;
51
1452-1462
MissingFormLabel
- 57
Dutton CM, Joba W, Spitzweg C, Heufelder AE, Bahn RS.
Thyrotropin receptor expression in adrenal, kidney, and thymus.
Thyroid.
1997;
7
879-884
MissingFormLabel
- 58
Rossi GP, Ganzaroli C, Cesari M, Maresca A, Plebani M, Nussdorfer GG, Pessina AC.
Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms
in primary aldosteronism and high-to-normal renin hypertension.
Cardiovasc Res.
2003;
57
277-283
MissingFormLabel
- 59
Lacroix A, Hamet P, Boutin JM.
Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome.
N Engl J Med.
1999;
341
1577-1581
MissingFormLabel
- 60
Reznik Y, Lefebvre H, Rohmer V, Charbonnel B, Tabarin A, Rodien P, Lecomte P, Bardet S, Coffin C, Mahoudeau J.
Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with
subclinical autonomous cortisol hypersecretion: a prospective clinical study.
Clin Endocrinol (Oxf).
2004;
61
311-319
MissingFormLabel
- 61
Born-Frontsberg E, Reincke M, Beuschlein F, Quinkler M.
Tumor size of Conn's adenoma and comorbidities.
Horm Metab Res.
2009;
41
785-788
MissingFormLabel
- 62
Mazzuco TL, Chaffanjon P, Martinie M, Sturm N, Chabre O.
Adrenal Cushing's Syndrome Due to Bilateral Macronodular Adrenal Hyperplasia: Prediction
of the Efficacy of beta-blockade Therapy and Interest of Unilateral Adrenalectomy.
Endocr J.
2009;
56
867-877
MissingFormLabel
Correspondence
A. LacroixMD
Professor of Medicine
Hôtel-Dieu du CHUM
3840 Saint-Urbain Street
Montréal, Québec
Canada, H2W 1T8
Phone: +1 514 890 8000 (ext. 14930)
Fax: +1 514 412 7128
Email: andre.lacroix@umontreal.ca