KEGG   PATHWAY: mna04927
mna04927                    Pathway                                

Cortisol synthesis and secretion - Miniopterus natalensis
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
Pathway map
mna04927  Cortisol synthesis and secretion

Other DBs
GO: 0043400
Miniopterus natalensis [GN:mna]
107525239  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
107533496  MRAP; melanocortin-2 receptor accessory protein [KO:K22398]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107535074  PDE8B; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B [KO:K18437] [EC:]
107539243  PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A [KO:K18437] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107543674  NR0B1; nuclear receptor subfamily 0 group B member 1 [KO:K08562]
107535479  steroidogenic factor 1 [KO:K08560]
107528285  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
107528307  SP1; transcription factor Sp1 [KO:K04684]
107537943  PBX1; pre-B-cell leukemia transcription factor 1 [KO:K09355]
107524712  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107532468  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
107531265  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107525737  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107543873  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107530327  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107544136  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
107544933  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107544390  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
107539006  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
107542744  cytochrome P450 11B1, mitochondrial-like isoform X1 [KO:K00497] [EC:]
107542528  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:]
107535187  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
107533528  NCEH1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
107524243  AGT; angiotensinogen [KO:K09821]
107544042  AGTR1; type-1 angiotensin II receptor [KO:K04166]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107544328  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107546296  KCNK2; potassium channel subfamily K member 2 [KO:K04913]
107529836  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
107533412  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
107531235  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
107546425  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
107534931  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
107541372  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
107536018  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
107529588  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
107531917  KCNA4; potassium voltage-gated channel subfamily A member 4 [KO:K04877]
107534793  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
107533280  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
107529684  SCARB1; scavenger receptor class B member 1 [KO:K13885]
107535212  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:]
107545288  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:]
107538945  steroid 21-hydroxylase [KO:K00513] [EC:]
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
Endotext (2000)
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)
mna00140  Steroid hormone biosynthesis
mna04020  Calcium signaling pathway
mna04024  cAMP signaling pathway
mna04960  Aldosterone-regulated sodium reabsorption
KO pathway

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