KEGG   PATHWAY: mlx04925
Entry
mlx04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Mirounga leonina (Southern elephant seal)
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
mlx04925  Aldosterone synthesis and secretion
mlx04925

Other DBs
GO: 0035932
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997950  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
117997993  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
117998053  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
117998176  CALM3; calmodulin-3 [KO:K02183]
117998180  PRKD2; serine/threonine-protein kinase D2 isoform X1 [KO:K06070] [EC:2.7.11.13]
117998504  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
117998657  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117998905  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
117999123  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117999337  DAGLB; sn1-specific diacylglycerol lipase beta [KO:K13806] [EC:3.1.1.116]
118000178  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540]
118000481  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
118000525  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
118001326  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
118002566  CALM1; calmodulin-1 [KO:K02183]
118002976  PRKD1; serine/threonine-protein kinase D1 [KO:K06070] [EC:2.7.11.13]
118003004  [KO:K01540]
118003092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118003137  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
118003325  [KO:K00498] [EC:1.14.15.6]
118003693  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
118004307  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
118004626  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
118004937  AGTR1; type-1 angiotensin II receptor [KO:K04166]
118005070  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118005092  ATP2B2; plasma membrane calcium-transporting ATPase 2 [KO:K05850] [EC:7.2.2.10]
118005189  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
118005236  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118005532  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
118005983  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
118006021  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
118006050  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
118006264  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
118006598  [KO:K04515] [EC:2.7.11.17]
118006728  [KO:K04515] [EC:2.7.11.17]
118007016  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
118007404  POMC; pro-opiomelanocortin [KO:K05228]
118007652  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
118007675  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
118007768  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
118008161  CALM2; calmodulin-2 [KO:K02183]
118008176  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
118008825  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
118008851  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
118008901  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
118008972  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
118009168  [KO:K09053]
118009964  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
118011244  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011247  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118012101  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
118012308  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
118012432  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
118012453  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
118012486  [KO:K02183]
118012894  AGT; angiotensinogen [KO:K09821]
118013394  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
118013821  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
118013832  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
118013976  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
118013977  [KO:K01539] [EC:7.2.2.13]
118014170  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
118014221  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
118014278  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X1 [KO:K08794] [EC:2.7.11.17]
118014510  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
118014792  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
118014964  ATP2B3; plasma membrane calcium-transporting ATPase 3 [KO:K05850] [EC:7.2.2.10]
118015219  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
118015807  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
118015920  DAGLA; sn1-specific diacylglycerol lipase alpha [KO:K13806] [EC:3.1.1.116]
118015997  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118016419  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
118016596  [KO:K02183]
118017609  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
118017967  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
118018382  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
118018437  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
118019227  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118019658  CALML6; calmodulin-like protein 6 [KO:K02183]
118020338  NPPA; natriuretic peptides A [KO:K12334]
118020691  [KO:K02183]
118021134  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
118021299  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
118021581  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
118021620  CALML3; calmodulin-like protein 3 [KO:K02183]
118021683  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
118021697  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118021775  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
118021903  [KO:K02183]
118023087  [KO:K04632]
118023800  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118024008  [KO:K04632]
118024010  [KO:K04632]
118024347  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118024497  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
118024512  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118024757  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
118025560  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118025809  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
118026266  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118027107  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
118027308  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
118027311  [KO:K00513] [EC:1.14.14.16]
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
mlx00140  Steroid hormone biosynthesis
mlx00590  Arachidonic acid metabolism
mlx04020  Calcium signaling pathway
mlx04022  cGMP-PKG signaling pathway
mlx04024  cAMP signaling pathway
mlx04614  Renin-angiotensin system
mlx04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

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