KEGG   PATHWAY: lve04925
Entry
lve04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Lipotes vexillifer (Yangtze River dolphin)
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
lve04925  Aldosterone synthesis and secretion
lve04925

Other DBs
GO: 0035932
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103068522  CACNA1I; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
103068564  [KO:K00498] [EC:1.14.15.6]
103068907  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
103068908  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
103068913  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
103069101  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103069558  [KO:K00513] [EC:1.14.14.16]
103070387  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103070451  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103070583  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
103070670  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
103071696  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103072156  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
103072903  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
103073028  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103073180  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
103074112  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103074371  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
103074541  [KO:K02183]
103074544  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103074607  LIPE; hormone-sensitive lipase [KO:K07188] [EC:3.1.1.79]
103074614  ATP1A4; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
103074817  CALML5; calmodulin-like protein 5 [KO:K02183]
103074894  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
103075153  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103075213  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103075234  DAGLB; sn1-specific diacylglycerol lipase beta isoform X1 [KO:K13806] [EC:3.1.1.116]
103075255  CAMK1; calcium/calmodulin-dependent protein kinase type 1 [KO:K08794] [EC:2.7.11.17]
103075325  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
103075499  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103075978  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
103076182  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103076924  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
103077071  NR4A1; nuclear receptor subfamily 4 group A member 1 isoform X1 [KO:K04465]
103077184  POMC; pro-opiomelanocortin [KO:K05228]
103077464  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103077803  CACNA1H; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
103078157  AGT; angiotensinogen [KO:K09821]
103078639  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103078677  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103078697  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103078806  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
103079287  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103079294  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
103079915  CALML6; calmodulin-like protein 6 [KO:K02183]
103080153  NPPA; natriuretic peptides A [KO:K12334]
103080762  CALM1; calmodulin isoform X1 [KO:K02183]
103081119  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
103081345  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
103081366  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
103081539  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103081811  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
103082192  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103082420  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103083046  [KO:K00070] [EC:1.1.1.145 5.3.3.1]
103083306  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103083354  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
103083884  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
103083957  MC2R; adrenocorticotropic hormone receptor isoform X1 [KO:K04200]
103084165  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
103084302  ATF1; cyclic AMP-dependent transcription factor ATF-1 [KO:K09053]
103084463  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
103084817  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
103084901  DAGLA; sn1-specific diacylglycerol lipase alpha [KO:K13806] [EC:3.1.1.116]
103085203  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
103085385  [KO:K04632]
103085693  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103085711  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103085845  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103086171  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103086280  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103086653  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103087008  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103087340  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103087450  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X1 [KO:K08794] [EC:2.7.11.17]
103087479  CALM2; calmodulin [KO:K02183]
103087689  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
103088376  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
103088382  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
103088391  LDLR; low-density lipoprotein receptor [KO:K12473]
103088422  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
103088458  CAMK2D; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
103088806  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
103089051  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
103089070  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103089387  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
103089542  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
103089616  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103090123  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D [KO:K08794] [EC:2.7.11.17]
103090549  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103090575  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103090648  AGTR1; type-1 angiotensin II receptor [KO:K04166]
103090978  PRKD1; serine/threonine-protein kinase D1-like [KO:K06070] [EC:2.7.11.13]
103091030  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
103091169  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
103091655  CALM3; calmodulin [KO:K02183]
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
lve00140  Steroid hormone biosynthesis
lve00590  Arachidonic acid metabolism
lve04020  Calcium signaling pathway
lve04022  cGMP-PKG signaling pathway
lve04024  cAMP signaling pathway
lve04614  Renin-angiotensin system
lve04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

DBGET integrated database retrieval system