Entry
Name
Aldosterone synthesis and secretion - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa04925 Aldosterone synthesis and secretion
Ortholog table
Network
Element
N00301 Angiotensin-aldosterone signaling pathway
Drug
D00146 Corticotropin (USP/INN)
D01238 Bucladesine sodium (JAN)
D02105 Tetracosactide acetate (JAN)
D03593 Corticotropin zinc hydroxide
D05801 Saprisartan potassium (USAN)
D05827 Seractide acetate (USAN)
D06544 Corticotropin, repository (USP)
D09801 Giractide acetate (JAN)
D11061 Osilodrostat (USAN/INN)
D11062 Osilodrostat phosphate (JAN/USAN)
D12773 Lorundrostat (USAN/INN)
D12774 Lorundrostat hydrobromide (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
185 AGTR1; angiotensin II receptor type 1 [KO:K04166 ]
2767 GNA11; G protein subunit alpha 11 [KO:K04635 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
1388 ATF6B; activating transcription factor 6 beta [KO:K09049 ]
466 ATF1; activating transcription factor 1 [KO:K09053 ]
3777 KCNK3; potassium two pore domain channel subfamily K member 3 [KO:K04914 ]
51305 KCNK9; potassium two pore domain channel subfamily K member 9 [KO:K04919 ]
3762 KCNJ5; potassium inwardly rectifying channel subfamily J member 5 [KO:K04999 ]
23439 ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540 ]
481 ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540 ]
482 ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540 ]
483 ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540 ]
8913 CACNA1G; calcium voltage-gated channel subunit alpha1 G [KO:K04854 ]
8912 CACNA1H; calcium voltage-gated channel subunit alpha1 H [KO:K04855 ]
8911 CACNA1I; calcium voltage-gated channel subunit alpha1 I [KO:K04856 ]
775 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850 ]
776 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
778 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853 ]
779 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857 ]
84876 ORAI1; ORAI calcium release-activated calcium modulator 1 [KO:K16056 ]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515 ] [EC:2.7.11.17 ]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515 ] [EC:2.7.11.17 ]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515 ] [EC:2.7.11.17 ]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515 ] [EC:2.7.11.17 ]
3949 LDLR; low density lipoprotein receptor [KO:K12473 ]
949 SCARB1; scavenger receptor class B member 1 [KO:K13885 ]
6770 STAR; steroidogenic acute regulatory protein [KO:K16931 ]
4929 NR4A2; nuclear receptor subfamily 4 group A member 2 [KO:K08558 ]
3164 NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465 ]
Compound
C01124 18-Hydroxycorticosterone
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Hattangady NG, Olala LO, Bollag WB, Rainey WE
Title
Acute and chronic regulation of aldosterone production.
Journal
Reference
Authors
Bollag WB
Title
Regulation of aldosterone synthesis and secretion.
Journal
Reference
Authors
Spat A, Hunyady L
Title
Control of aldosterone secretion: a model for convergence in cellular signaling pathways.
Journal
Reference
Authors
Boon WC, Coghlan JP, Curnow KM, McDougall JG
Title
Aldosterone secretion: a molecular perspective.
Journal
Reference
Authors
Bassett MH, Suzuki T, Sasano H, White PC, Rainey WE
Title
The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production.
Journal
Reference
Authors
Guagliardo NA, Yao J, Hu C, Barrett PQ
Title
Minireview: aldosterone biosynthesis: electrically gated for our protection.
Journal
Reference
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
Reference
Authors
Spat A, Szanda G
Title
Special features of mitochondrial Ca(2)(+) signalling in adrenal glomerulosa cells.
Journal
Reference
Authors
Tsai LC, Beavo JA
Title
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
Journal
Reference
Authors
Delcayre C, Silvestre JS
Title
Aldosterone and the heart: towards a physiological function?
Journal
Reference
Authors
Lisurek M, Bernhardt R
Title
Modulation of aldosterone and cortisol synthesis on the molecular level.
Journal
Reference
Authors
Miller WL
Title
Steroid hormone synthesis in mitochondria.
Journal
Reference
Authors
Martinez-Arguelles DB, Papadopoulos V
Title
Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland.
Journal
Related pathway
hsa04960 Aldosterone-regulated sodium reabsorption
KO pathway