KEGG   PATHWAY: chx04925
Entry
chx04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Capra hircus (goat)
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
chx04925  Aldosterone synthesis and secretion
chx04925

Other DBs
GO: 0035932
Organism
Capra hircus (goat) [GN:chx]
Gene
102187651  AGT; angiotensinogen [KO:K09821]
102174163  AGTR1; type-1 angiotensin II receptor [KO:K04166]
102189950  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102177328  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102188148  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102180505  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102169966  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102189653  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102188092  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102170858  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102184768  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102180890  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102172114  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
102175984  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102169016  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
102174216  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
106503372  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
102175981  PRKD2; serine/threonine-protein kinase D2 isoform X1 [KO:K06070] [EC:2.7.11.13]
102186065  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102180634  ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
102185072  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102180221  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
102174829  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102183745  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
102183893  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102170199  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
102190378  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102171671  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
102168976  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X3 [KO:K09053]
102170586  DAGLA; sn1-specific diacylglycerol lipase alpha [KO:K13806] [EC:3.1.1.116]
102173707  DAGLB; sn1-specific diacylglycerol lipase beta [KO:K13806] [EC:3.1.1.116]
106502632  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
102179786  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
102169739  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102179588  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
102183561  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
102186069  sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
102186539  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
102183405  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
102188357  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
102168373  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
108633809  sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
102191649  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
102187163  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
102185724  CACNA1I; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
100861292  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102174706  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102189746  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
102176151  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
102171809  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
102185007  CALM1; calmodulin [KO:K02183]
102172164  CALM2; calmodulin isoform X1 [KO:K02183]
102175311  calmodulin [KO:K02183]
106502751  calmodulin-like protein 3 [KO:K02183]
102187248  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
102169697  CALM3; calmodulin [KO:K02183]
102171428  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102174671  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
102185318  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
102168659  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X1 [KO:K08794] [EC:2.7.11.17]
102176762  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102185715  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
102185084  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102175934  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102187484  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
102168898  ATP2B3; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
102176524  plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
102187815  ATP2B2; LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
102174093  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100860801  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
102186579  LDLR; low-density lipoprotein receptor [KO:K12473]
102178475  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
102182514  POMC; pro-opiomelanocortin [KO:K05228]
102182364  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
102188874  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
108633189  neuroendocrine secretory protein 55 [KO:K04632]
102180724  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
102171922  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102169019  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102185469  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
102189798  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102169557  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102185858  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102184919  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102188104  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102173379  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102168790  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102187294  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
102169808  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
102185438  NR4A1; nuclear receptor subfamily 4 group A member 1 isoform X1 [KO:K04465]
102173131  CYP11A1; cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
100860869  3BHSD; 3beta-hydroxysteroid dehydrogenase/isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
102174710  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
102181974  NPPA; natriuretic peptides A precursor [KO:K12334]
102186447  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
102179217  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase [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
chx00140  Steroid hormone biosynthesis
chx00590  Arachidonic acid metabolism
chx04020  Calcium signaling pathway
chx04022  cGMP-PKG signaling pathway
chx04024  cAMP signaling pathway
chx04614  Renin-angiotensin system
chx04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
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