KEGG   PATHWAY: cge04925
Entry
cge04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Cricetulus griseus (Chinese hamster)
Description
Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone plays an important role in the regulation of systemic blood pressure through the absorption of sodium and water. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main extracellular stimuli which regulate aldosterone secretion. These physiological agonists all converge on two major intracellular signaling pathways: calcium (Ca2+) mobilization and an increase in cAMP production. The increase in cytosolic calcium levels activates calcium/calmodulin- dependent protein kinases (CaMK), and the increased cAMP levels stimulate the activity of cAMP-dependent protein kinase, or protein kinase A (PKA). The activated CaMK, and possibly PKA, activates transcription factors (NURR1 and NGF1B, CREB) to induce StAR and CYP11B2 expression, the early and late rate- limiting steps in aldosterone biosynthesis, respectively, thereby stimulating aldosterone secretion.
Class
Organismal Systems; Endocrine system
Pathway map
cge04925  Aldosterone synthesis and secretion
cge04925

Other DBs
GO: 0035932
Organism
Cricetulus griseus (Chinese hamster) [GN:cge]
Gene
100773858  Agt; angiotensinogen [KO:K09821]
100755233  type-1A angiotensin II receptor [KO:K04166]
100750798  Agtr1; type-1 angiotensin II receptor [KO:K04166]
100689066  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100689065  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
100760134  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
100760731  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100770957  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100751979  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
100764450  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X9 [KO:K04958]
100758965  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
100751775  inositol 1,4,5-trisphosphate receptor type 3 isoform X3 [KO:K04960]
100766006  Prkca; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
100760922  Prkcb; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100762950  Prkcg; protein kinase C gamma type isoform X2 [KO:K19663] [EC:2.7.11.13]
100763552  Prkce; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100763335  Prkd2; serine/threonine-protein kinase D2 isoform X2 [KO:K06070] [EC:2.7.11.13]
100762119  Prkd1; serine/threonine-protein kinase D1 isoform X4 [KO:K06070] [EC:2.7.11.13]
100756168  Prkd3; serine/threonine-protein kinase D3 isoform X1 [KO:K06070] [EC:2.7.11.13]
100761582  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100754663  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100689386  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100762192  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
100771872  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
100766300  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100774488  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100772940  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100764159  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
100767112  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049]
100773050  Atf1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
100765603  Daglb; diacylglycerol lipase-beta isoform X1 [KO:K13806] [EC:3.1.1.116]
100756392  Dagla; sn1-specific diacylglycerol lipase alpha isoform X1 [KO:K13806] [EC:3.1.1.116]
100771641  Kcnk3; potassium channel subfamily K member 3 isoform X2 [KO:K04914]
100756282  Kcnk9; potassium channel subfamily K member 9 isoform X2 [KO:K04919]
100766874  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100771378  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X2 [KO:K01539] [EC:7.2.2.13]
100763478  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100763191  Atp1a4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100758209  Atp1a3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-3 isoform X2 [KO:K01539] [EC:7.2.2.13]
100765669  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 isoform X2 [KO:K01540]
100762833  Atp1b4; protein ATP1B4 isoform X3 [KO:K01540]
100760718  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100757379  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 isoform X2 [KO:K01540]
100761932  Cacna1g; voltage-dependent T-type calcium channel subunit alpha-1G isoform X9 [KO:K04854]
100762221  Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H isoform X2 [KO:K04855]
100769169  voltage-dependent T-type calcium channel subunit alpha-1I isoform X4 [KO:K04856]
100754788  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X30 [KO:K04850]
100772497  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100757994  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F isoform X2 [KO:K04853]
100765508  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S isoform X5 [KO:K04857]
100752394  Orai1; calcium release-activated calcium channel protein 1 isoform X2 [KO:K16056]
100766751  Calml3; calmodulin-like protein 3 [KO:K02183]
100767046  Calml5; calmodulin-like protein 5 isoform X1 [KO:K02183]
100762749  Calm3; calmodulin-3 isoform X2 [KO:K02183]
100765281  Calm2; calmodulin-2 isoform X2 [KO:K02183]
100771772  Calm1; calmodulin-1 isoform X2 [KO:K02183]
100757500  Calml4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100751814  calmodulin-like isoform X2 [KO:K02183]
100755149  Camk1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
100763374  Camk1g; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
100769205  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
100763272  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515] [EC:2.7.11.17]
100752268  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
100765253  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X3 [KO:K04515] [EC:2.7.11.17]
100774010  Camk4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
100764066  Atp2b1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100753233  Atp2b3; plasma membrane calcium-transporting ATPase 3 isoform X2 [KO:K05850] [EC:7.2.2.10]
100759670  Atp2b2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
100764868  Atp2b4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
100755300  Lipe; hormone-sensitive lipase isoform X2 [KO:K07188] [EC:3.1.1.79]
100689399  Ldlr; low-density lipoprotein receptor precursor [KO:K12473]
100736552  Scarb1; scavenger receptor class B member 1 [KO:K13885]
100756311  Pomc; pro-opiomelanocortin isoform X2 [KO:K05228]
100757427  Mc2r; adrenocorticotropic hormone receptor [KO:K04200]
100689067  Gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103158534  neuroendocrine secretory protein 55 [KO:K04632]
100764561  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100773811  Adcy2; adenylate cyclase type 2 isoform X2 [KO:K08042] [EC:4.6.1.1]
100770498  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100768998  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100765958  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
100768368  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100756132  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
113837458  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100751372  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100768997  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100767097  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100771651  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
100766422  Nr4a2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
100764218  Nr4a1; nuclear receptor subfamily 4 group A member 1 isoform X2 [KO:K04465]
100752606  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
100770922  NADPH-dependent 3-keto-steroid reductase HSD3B3 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
113833179  LOW QUALITY PROTEIN: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like isoform X2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
113833198  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
113830678  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 isoform X2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100767691  steroid 21-hydroxylase isoform X2 [KO:K00513] [EC:1.14.14.16]
100774350  Nppa; natriuretic peptides A [KO:K12334]
100752423  Npr1; atrial natriuretic peptide receptor 1 isoform X3 [KO:K12323] [EC:4.6.1.2]
100750420  Pde2a; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X4 [KO:K18283] [EC:3.1.4.17]
Compound
C00003  NAD+
C00004  NADH
C00005  NADPH
C00006  NADP+
C00020  AMP
C00076  Calcium cation
C00165  Diacylglycerol
C00187  Cholesterol
C00219  Arachidonate
C00238  Potassium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01124  18-Hydroxycorticosterone
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01780  Aldosterone
C01953  Pregnenolone
C02140  Corticosterone
C03205  11-Deoxycorticosterone
C14777  12(S)-HETE
C14822  12(R)-HETE
Reference
PMID:21839803
  Authors
Hattangady NG, Olala LO, Bollag WB, Rainey WE
  Title
Acute and chronic regulation of aldosterone production.
  Journal
Mol Cell Endocrinol 350:151-62 (2012)
DOI:10.1016/j.mce.2011.07.034
Reference
PMID:24944029
  Authors
Bollag WB
  Title
Regulation of aldosterone synthesis and secretion.
  Journal
Compr Physiol 4:1017-55 (2014)
DOI:10.1002/cphy.c130037
Reference
PMID:15044681
  Authors
Spat A, Hunyady L
  Title
Control of aldosterone secretion: a model for convergence in cellular signaling pathways.
  Journal
Physiol Rev 84:489-539 (2004)
DOI:10.1152/physrev.00030.2003
Reference
PMID:18406824
  Authors
Boon WC, Coghlan JP, Curnow KM, McDougall JG
  Title
Aldosterone secretion: a molecular perspective.
  Journal
Trends Endocrinol Metab 8:346-54 (1997)
DOI:10.1016/S1043-2760(97)00136-7
Reference
PMID:14645496
  Authors
Bassett MH, Suzuki T, Sasano H, White PC, Rainey WE
  Title
The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production.
  Journal
Mol Endocrinol 18:279-90 (2004)
DOI:10.1210/me.2003-0005
Reference
PMID:22689262
  Authors
Guagliardo NA, Yao J, Hu C, Barrett PQ
  Title
Minireview: aldosterone biosynthesis: electrically gated for our protection.
  Journal
Endocrinology 153:3579-86 (2012)
DOI:10.1210/en.2012-1339
Reference
PMID:22364774
  Authors
Spat A, Fulop L, Szanda G
  Title
The role of mitochondrial Ca(2+) and NAD(P)H in the control of aldosterone secretion.
  Journal
Cell Calcium 52:64-72 (2012)
DOI:10.1016/j.ceca.2012.01.009
Reference
PMID:22395411
  Authors
Spat A, Szanda G
  Title
Special features of mitochondrial Ca(2)(+) signalling in adrenal glomerulosa cells.
  Journal
Pflugers Arch 464:43-50 (2012)
DOI:10.1007/s00424-012-1086-y
Reference
PMID:21962440
  Authors
Tsai LC, Beavo JA
  Title
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
  Journal
Curr Opin Pharmacol 11:670-5 (2011)
DOI:10.1016/j.coph.2011.09.003
Reference
PMID:10536682
  Authors
Delcayre C, Silvestre JS
  Title
Aldosterone and the heart: towards a physiological function?
  Journal
Cardiovasc Res 43:7-12 (1999)
DOI:10.1016/S0008-6363(99)00088-7
Reference
PMID:15026188
  Authors
Lisurek M, Bernhardt R
  Title
Modulation of aldosterone and cortisol synthesis on the molecular level.
  Journal
Mol Cell Endocrinol 215:149-59 (2004)
DOI:10.1016/j.mce.2003.11.008
Reference
PMID:23628605
  Authors
Miller WL
  Title
Steroid hormone synthesis in mitochondria.
  Journal
Mol Cell Endocrinol 379:62-73 (2013)
DOI:10.1016/j.mce.2013.04.014
Reference
PMID:25788893
  Authors
Martinez-Arguelles DB, Papadopoulos V
  Title
Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland.
  Journal
Front Endocrinol (Lausanne) 6:29 (2015)
DOI:10.3389/fendo.2015.00029
Related
pathway
cge00140  Steroid hormone biosynthesis
cge00590  Arachidonic acid metabolism
cge04020  Calcium signaling pathway
cge04022  cGMP-PKG signaling pathway
cge04024  cAMP signaling pathway
cge04614  Renin-angiotensin system
cge04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
LinkDB

DBGET integrated database retrieval system