KEGG   PATHWAY: biu04925
Entry
biu04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Bos indicus (zebu cattle)
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
biu04925  Aldosterone synthesis and secretion
biu04925

Other DBs
GO: 0035932
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109553744  AGT; angiotensinogen [KO:K09821]
109559421  AGTR1; type-1 angiotensin II receptor [KO:K04166]
109562978  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
109561778  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
109554384  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
109567852  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109567854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109564927  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109576135  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109558547  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109576552  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109573366  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
109578560  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109572998  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109566044  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
109572710  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
109575479  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
109565980  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
109570093  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
109566270  ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
109559832  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109554418  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
109557676  CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
109563018  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
109569868  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
109561750  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
109557489  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
109576848  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
109559109  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
109554533  DAGLA; sn1-specific diacylglycerol lipase alpha [KO:K13806] [EC:3.1.1.116]
109578363  DAGLB; sn1-specific diacylglycerol lipase beta [KO:K13806] [EC:3.1.1.116]
109565592  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
109568182  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
109554202  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
109578704  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
109578722  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
109555876  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
109571737  ATP1A3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
109555144  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
109574423  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
109570324  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
109559642  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
109574240  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
109578051  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
109558631  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
109558615  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
109576190  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
109554975  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
109571127  ORAI1; calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
109565417  CALM1; calmodulin [KO:K02183]
109575003  calmodulin-alpha-like [KO:K02183]
109566056  CALM2; calmodulin [KO:K02183]
109568081  calmodulin-like [KO:K02183]
109570679  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
109572535  CALM3; calmodulin isoform X1 [KO:K02183]
109564712  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
109567581  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D [KO:K08794] [EC:2.7.11.17]
109576206  CAMK1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
109570799  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
109553698  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109560236  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109557541  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109562200  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
109555546  ATP2B3; plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
109558967  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
109570406  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
109576121  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
109572731  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
109561609  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
109571356  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
109566326  POMC; pro-opiomelanocortin [KO:K05228]
109577760  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
109567291  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
109567292  neuroendocrine secretory protein 55 [KO:K04632]
109557525  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109574822  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109566330  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
109564199  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
109555842  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109559159  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
109572478  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109568647  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109578364  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
109556827  PRKACB; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109561498  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109553478  STAR; steroidogenic acute regulatory protein, mitochondrial isoform X1 [KO:K16931]
109567528  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
109559075  NR4A1; nuclear receptor subfamily 4 group A member 1 isoform X1 [KO:K04465]
109575664  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
109555859  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
109576856  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
109570145  NPPA; natriuretic peptides A [KO:K12334]
109554550  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
109569677  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [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
biu00140  Steroid hormone biosynthesis
biu00590  Arachidonic acid metabolism
biu04020  Calcium signaling pathway
biu04022  cGMP-PKG signaling pathway
biu04024  cAMP signaling pathway
biu04614  Renin-angiotensin system
biu04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
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