KEGG   PATHWAY: fca04927Help
fca04927                    Pathway                                

Cortisol synthesis and secretion - Felis catus (domestic cat)
Cortisol is the main endogenous glucocorticoid, which affects a plethora of physiological functions, e.g., lipid and glucose metabolism, metabolic homeostasis and adaptation to stress. Cortisol production is primarily regulated by corticotropin (ACTH) in zona fasciculata. The stimulatory effect of ACTH on cortisol synthesis depends on cAMP dependent signaling, but also involves membrane depolarization and increased cytosolic Ca2+. Each of cAMP and Ca2+ induces the expression of StAR, stimulating intramitochondrial cholesterol transfer, as well as the steroidogenic enzymes in the pathway from cholesterol to cortisol (e.g., CHE, CYP17A1, CYP11B1).
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
fca04927  Cortisol synthesis and secretion

Ortholog table
Other DBs
GO: 0043400
Felis catus (domestic cat) [GN:fca]
101087223  POMC; pro-opiomelanocortin [KO:K05228]
692350  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
101093795  MRAP; melanocortin-2 receptor accessory protein isoform X2 [KO:K22398]
101098453  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
101097735  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
101091211  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:]
101094148  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
101083652  PDE8B; LOW QUALITY PROTEIN: high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B [KO:K18437] [EC:]
101086313  PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1 [KO:K18437] [EC:]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
101100624  NR0B1; nuclear receptor subfamily 0 group B member 1 [KO:K08562]
111556260  NR5A1; steroidogenic factor 1 [KO:K08560]
101097902  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
101100227  SP1; transcription factor Sp1 [KO:K04684]
101081781  PBX1; pre-B-cell leukemia transcription factor 1 isoform X1 [KO:K09355]
101090884  ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
101084297  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101089838  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101100293  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101100442  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
101093555  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101087097  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101084784  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X7 [KO:K09047]
101094849  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X4 [KO:K09049]
101097790  cytochrome P450 11B1, mitochondrial [KO:K00497] [EC:]
493967  CYP17A1; steroid 17-alpha-hydroxylase/17,20 lyase precursor [KO:K00512] [EC:]
100616071  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
101082846  NCEH1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
101093714  AGT; angiotensinogen [KO:K09821]
101082936  AGTR1; type-1 angiotensin II receptor [KO:K04166]
101094708  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101086541  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101087993  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101096695  KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
101098757  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
101090071  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
101097569  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856]
101088394  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X12 [KO:K04851]
101080870  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101096922  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
101084479  KCNA4; potassium voltage-gated channel subfamily A member 4 [KO:K04877]
101082745  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
101080362  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
101083715  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
101085980  cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:]
100616070  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:]
101094596  steroid 21-hydroxylase [KO:K00513] [EC:]
101082923  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C
101087555  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
101088157  ADCY3; adenylate cyclase type 3 isoform X1
101090005  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
101090942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:]
101091299  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X3
101092262  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
101092961  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:]
101094327  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:]
101095942  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X3
101100749  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:]
101101375  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
654399  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
C00020  AMP
C00076  Calcium cation
C00187  Cholesterol
C00238  Potassium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C00735  Cortisol
C01176  17alpha-Hydroxyprogesterone
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01953  Pregnenolone
C05138  17alpha-Hydroxypregnenolone
C05488  11-Deoxycortisol
Gallo-Payet N, Battista MC
Steroidogenesis-adrenal cell signal transduction.
Compr Physiol 4:889-964 (2014)
Enyeart JJ
Biochemical and Ionic signaling mechanisms for ACTH-stimulated cortisol production.
Vitam Horm 70:265-79 (2005)
Bandulik S, Tauber P, Lalli E, Barhanin J, Warth R
Two-pore domain potassium channels in the adrenal cortex.
Pflugers Arch 467:1027-42 (2015)
Liu H, Enyeart JA, Enyeart JJ
Angiotensin II inhibits native bTREK-1 K+ channels through a PLC-, kinase C-, and PIP2-independent pathway requiring ATP hydrolysis.
Am J Physiol Cell Physiol 293:C682-95 (2007)
Enyeart JJ, Danthi SJ, Liu H, Enyeart JA
Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate Ca2+- and ATP hydrolysis-dependent mechanisms.
J Biol Chem 280:30814-28 (2005)
Shen WJ, Azhar S, Kraemer FB
ACTH Regulation of Adrenal SR-B1.
Front Endocrinol (Lausanne) 7:42 (2016)
Ruggiero C, Lalli E
Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes.
Front Endocrinol (Lausanne) 7:24 (2016)
Margioris AN, Tsatsanis C
ACTH Action on the Adrenals
Spiga F, Lightman SL
Dynamics of adrenal glucocorticoid steroidogenesis in health and disease.
Mol Cell Endocrinol 408:227-34 (2015)
Tsai LC, Beavo JA
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
Curr Opin Pharmacol 11:670-5 (2011)
Odermatt A, Strajhar P, Engeli RT
Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools.
J Steroid Biochem Mol Biol 158:9-21 (2016)
Manna PR, Stetson CL, Slominski AT, Pruitt K
Role of the steroidogenic acute regulatory protein in health and disease.
Endocrine 51:7-21 (2016)
Jackson DS, Ramachandrappa S, Clark AJ, Chan LF
Melanocortin receptor accessory proteins in adrenal disease and obesity.
Front Neurosci 9:213 (2015)
Cerda-Reverter JM, Agulleiro MJ, Cortes R, Sanchez E, Guillot R, Leal E, Fernandez-Duran B, Puchol S, Eley M
Involvement of melanocortin receptor accessory proteins (MRAPs) in the function of melanocortin receptors.
Gen Comp Endocrinol 188:133-6 (2013)
Enyeart JJ, Enyeart JA
Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: properties and modulation by ACTH and AngII.
J Gen Physiol 142:137-55 (2013)
Midzak A, Papadopoulos V
Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies.
Front Endocrinol (Lausanne) 7:106 (2016)
Calebiro D, Di Dalmazi G, Bathon K, Ronchi CL, Beuschlein F
cAMP signaling in cortisol-producing adrenal adenoma.
Eur J Endocrinol 173:M99-106 (2015)
Turcu AF, Auchus RJ
Adrenal steroidogenesis and congenital adrenal hyperplasia.
Endocrinol Metab Clin North Am 44:275-96 (2015)
fca00140  Steroid hormone biosynthesis
fca04020  Calcium signaling pathway
fca04024  cAMP signaling pathway
fca04960  Aldosterone-regulated sodium reabsorption
KO pathway

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