KEGG   PATHWAY: mun04927
Entry
mun04927                    Pathway                                
Name
Cortisol synthesis and secretion - Meriones unguiculatus (Mongolian gerbil)
Description
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).
Class
Organismal Systems; Endocrine system
Pathway map
mun04927  Cortisol synthesis and secretion
mun04927

Other DBs
GO: 0043400
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110555189  Pomc; pro-opiomelanocortin [KO:K05228]
110562156  Mc2r; adrenocorticotropic hormone receptor [KO:K04200]
110541927  Mrap; melanocortin-2 receptor accessory protein isoform X1 [KO:K22398]
110563608  neuroendocrine secretory protein 55-like [KO:K04632]
110555169  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110550962  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
110555185  Adcy3; adenylate cyclase type 3 isoform X3 [KO:K08043] [EC:4.6.1.1]
110556521  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
110547229  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110559444  Adcy6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
110560723  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110561696  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110545944  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110540078  Pde8a; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A [KO:K18437] [EC:3.1.4.53]
110540896  Pde8b; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B isoform X1 [KO:K18437] [EC:3.1.4.53]
110545842  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110555016  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110543297  Nr0b1; nuclear receptor subfamily 0 group B member 1 [KO:K08562]
110546506  Nr5a1; steroidogenic factor 1 [KO:K08560]
110559141  Nr4a1; nuclear receptor subfamily 4immunitygroup A member 1 isoform X1 [KO:K04465]
110552322  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
110563863  Pbx1; pre-B-cell leukemia transcription factor 1 isoform X1 [KO:K09355]
110551437  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110556579  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
110564629  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110549859  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
110555614  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
110549233  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110554250  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110561882  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
110554970  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
110565383  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
110544545  cytochrome P450 11B1, mitochondrial-like [KO:K00497] [EC:1.14.15.4]
110562757  cytochrome P450 11B2, mitochondrial isoform X1 [KO:K00497] [EC:1.14.15.4]
110556807  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
110540823  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
110558664  Nceh1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
110555411  Agt; angiotensinogen isoform X3 [KO:K09821]
110539373  type-1 angiotensin II receptor [KO:K04166]
110563019  Agtr1; type-1 angiotensin II receptor [KO:K04166]
110562511  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110548534  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
110563159  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110555720  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110551595  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
110550598  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110552142  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
110558908  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110543748  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110553409  Kcnk2; potassium channel subfamily K member 2 isoform X1 [KO:K04913]
110552065  Cacna1g; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
110548671  Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
110550427  Cacna1i; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
110541273  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
110547567  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110561910  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
110548425  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
110545302  calcium release-activated calcium channel protein 1 [KO:K16056]
110565171  Kcna4; potassium voltage-gated channel subfamily A member 4 [KO:K04877]
110547673  Kcnk3; potassium channel subfamily K member 3 [KO:K04914]
110552462  Ldlr; low-density lipoprotein receptor isoform X1 [KO:K12473]
110554560  Scarb1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
110554825  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
110542496  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110543775  NADPH-dependent 3-keto-steroid reductase Hsd3b5-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110563733  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110563735  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656956  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656957  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656958  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 6-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110544899  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656961  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656962  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 6-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132656967  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
132657118  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110544885  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 6-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
110560117  steroid 21-hydroxylase isoform X1 [KO:K00513] [EC:1.14.14.16]
Compound
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
Reference
PMID:24944026
  Authors
Gallo-Payet N, Battista MC
  Title
Steroidogenesis-adrenal cell signal transduction.
  Journal
Compr Physiol 4:889-964 (2014)
DOI:10.1002/cphy.c130050
Reference
PMID:15727807
  Authors
Enyeart JJ
  Title
Biochemical and Ionic signaling mechanisms for ACTH-stimulated cortisol production.
  Journal
Vitam Horm 70:265-79 (2005)
DOI:10.1016/S0083-6729(05)70008-X
Reference
PMID:25339223
  Authors
Bandulik S, Tauber P, Lalli E, Barhanin J, Warth R
  Title
Two-pore domain potassium channels in the adrenal cortex.
  Journal
Pflugers Arch 467:1027-42 (2015)
DOI:10.1007/s00424-014-1628-6
Reference
PMID:17494631
  Authors
Liu H, Enyeart JA, Enyeart JJ
  Title
Angiotensin II inhibits native bTREK-1 K+ channels through a PLC-, kinase C-, and PIP2-independent pathway requiring ATP hydrolysis.
  Journal
Am J Physiol Cell Physiol 293:C682-95 (2007)
DOI:10.1152/ajpcell.00087.2007
Reference
PMID:15994319
  Authors
Enyeart JJ, Danthi SJ, Liu H, Enyeart JA
  Title
Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate Ca2+- and ATP hydrolysis-dependent mechanisms.
  Journal
J Biol Chem 280:30814-28 (2005)
DOI:10.1074/jbc.M504283200
Reference
PMID:27242666
  Authors
Shen WJ, Azhar S, Kraemer FB
  Title
ACTH Regulation of Adrenal SR-B1.
  Journal
Front Endocrinol (Lausanne) 7:42 (2016)
DOI:10.3389/fendo.2016.00042
Reference
PMID:27065945
  Authors
Ruggiero C, Lalli E
  Title
Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes.
  Journal
Front Endocrinol (Lausanne) 7:24 (2016)
DOI:10.3389/fendo.2016.00024
Reference
PMID:25905342
  Authors
Margioris AN, Tsatsanis C
  Title
ACTH Action on the Adrenals
  Journal
Endotext (2000)
Reference
PMID:25662280
  Authors
Spiga F, Lightman SL
  Title
Dynamics of adrenal glucocorticoid steroidogenesis in health and disease.
  Journal
Mol Cell Endocrinol 408:227-34 (2015)
DOI:10.1016/j.mce.2015.02.005
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:26807866
  Authors
Odermatt A, Strajhar P, Engeli RT
  Title
Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools.
  Journal
J Steroid Biochem Mol Biol 158:9-21 (2016)
DOI:10.1016/j.jsbmb.2016.01.009
Reference
PMID:26271515
  Authors
Manna PR, Stetson CL, Slominski AT, Pruitt K
  Title
Role of the steroidogenic acute regulatory protein in health and disease.
  Journal
Endocrine 51:7-21 (2016)
DOI:10.1007/s12020-015-0715-6
Reference
PMID:26113808
  Authors
Jackson DS, Ramachandrappa S, Clark AJ, Chan LF
  Title
Melanocortin receptor accessory proteins in adrenal disease and obesity.
  Journal
Front Neurosci 9:213 (2015)
DOI:10.3389/fnins.2015.00213
Reference
PMID:23410915
  Authors
Cerda-Reverter JM, Agulleiro MJ, Cortes R, Sanchez E, Guillot R, Leal E, Fernandez-Duran B, Puchol S, Eley M
  Title
Involvement of melanocortin receptor accessory proteins (MRAPs) in the function of melanocortin receptors.
  Journal
Gen Comp Endocrinol 188:133-6 (2013)
DOI:10.1016/j.ygcen.2013.01.017
Reference
PMID:23858003
  Authors
Enyeart JJ, Enyeart JA
  Title
Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: properties and modulation by ACTH and AngII.
  Journal
J Gen Physiol 142:137-55 (2013)
DOI:10.1085/jgp.201310964
Reference
PMID:27524977
  Authors
Midzak A, Papadopoulos V
  Title
Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies.
  Journal
Front Endocrinol (Lausanne) 7:106 (2016)
DOI:10.3389/fendo.2016.00106
Reference
PMID:26139209
  Authors
Calebiro D, Di Dalmazi G, Bathon K, Ronchi CL, Beuschlein F
  Title
cAMP signaling in cortisol-producing adrenal adenoma.
  Journal
Eur J Endocrinol 173:M99-106 (2015)
DOI:10.1530/EJE-15-0353
Reference
PMID:26038201
  Authors
Turcu AF, Auchus RJ
  Title
Adrenal steroidogenesis and congenital adrenal hyperplasia.
  Journal
Endocrinol Metab Clin North Am 44:275-96 (2015)
DOI:10.1016/j.ecl.2015.02.002
Related
pathway
mun00140  Steroid hormone biosynthesis
mun04020  Calcium signaling pathway
mun04024  cAMP signaling pathway
mun04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04927   
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