KEGG   PATHWAY: pleu04925
Entry
pleu04925                   Pathway                                
Name
Aldosterone synthesis and secretion - Peromyscus leucopus (white-footed mouse)
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
pleu04925  Aldosterone synthesis and secretion
pleu04925

Other DBs
GO: 0035932
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114681218  Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H isoform X2 [KO:K04855]
114681359  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
114681418  Calm3; calmodulin-3 [KO:K02183]
114681434  Prkd2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
114682025  [KO:K04632]
114682029  [KO:K04632]
114682227  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114683299  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
114683572  [KO:K06070] [EC:2.7.11.13]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114685348  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
114685349  Lipe; hormone-sensitive lipase isoform X3 [KO:K07188] [EC:3.1.1.79]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114686251  Agtr1; type-1 angiotensin II receptor [KO:K04166]
114687523  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
114687991  [KO:K04374]
114688126  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114688160  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
114688199  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688619  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688620  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688621  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688750  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688751  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114688752  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114689600  Camk1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
114689622  Atp2b2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
114689726  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114689941  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
114690210  Mc2r; LOW QUALITY PROTEIN: adrenocorticotropic hormone receptor [KO:K04200]
114690350  [KO:K00498] [EC:1.14.15.6]
114690439  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114690690  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
114690694  [KO:K01539] [EC:7.2.2.13]
114690974  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
114691010  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
114691636  Camk4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
114691640  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
114691978  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114692203  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114692885  Cacna1g; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
114693172  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114693978  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X7 [KO:K04515] [EC:2.7.11.17]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114694287  Cacna1i; voltage-dependent T-type calcium channel subunit alpha-1I isoform X3 [KO:K04856]
114695236  Ldlr; low-density lipoprotein receptor [KO:K12473]
114695785  [KO:K06070] [EC:2.7.11.13]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114696431  Nr4a2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
114696574  Kcnk3; potassium channel subfamily K member 3 [KO:K04914]
114696655  Nr4a1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
114696675  Atf1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
114696911  [KO:K04634]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114697442  Pomc; pro-opiomelanocortin [KO:K05228]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114698097  Atp2b4; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114698547  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114698572  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
114698742  Pde2a; LOW QUALITY PROTEIN: cGMP-dependent 3',5'-cyclic phosphodiesterase [KO:K18283] [EC:3.1.4.17]
114699702  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114699783  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
114700207  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114700762  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850]
114700827  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114701075  [KO:K04166]
114701199  Atp2b1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
114701281  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
114702318  [KO:K05850] [EC:7.2.2.10]
114702392  Camk1g; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
114703207  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114703432  Dagla; diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114704466  Prkd1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
114704549  Orai1; calcium release-activated calcium channel protein 1 isoform X1 [KO:K16056]
114704655  Kcnk9; potassium channel subfamily K member 9 [KO:K04919]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114705020  Calm1; calmodulin-1 [KO:K02183]
114705057  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114705847  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
114705894  [KO:K00513] [EC:1.14.14.16]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114706123  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114706243  Atp2b3; plasma membrane calcium-transporting ATPase 3 isoform X2 [KO:K05850] [EC:7.2.2.10]
114707150  Agt; angiotensinogen [KO:K09821]
114707396  Camk2a; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
114707579  Daglb; LOW QUALITY PROTEIN: diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
114707907  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
114707921  Npr1; LOW QUALITY PROTEIN: atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
114708260  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
114708393  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114708480  Camk1d; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114708768  [KO:K02183]
114708779  Calml3; calmodulin-like protein 3 [KO:K02183]
114709090  Prkce; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
114709209  Calm2; calmodulin-2 [KO:K02183]
114709654  Nppa; natriuretic peptides A [KO:K12334]
114709764  Atp1b4; protein ATP1B4 isoform X1 [KO:K01540]
114710198  Scarb1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
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
pleu00140  Steroid hormone biosynthesis
pleu00590  Arachidonic acid metabolism
pleu04020  Calcium signaling pathway
pleu04022  cGMP-PKG signaling pathway
pleu04024  cAMP signaling pathway
pleu04614  Renin-angiotensin system
pleu04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

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