KEGG   PATHWAY: hgl04927
Entry
hgl04927                    Pathway                                
Name
Cortisol synthesis and secretion - Heterocephalus glaber (naked mole-rat)
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
hgl04927  Cortisol synthesis and secretion
hgl04927

Other DBs
GO: 0043400
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101718053  Pomc; proopiomelanocortin [KO:K05228]
101699946  Mc2r; melanocortin 2 receptor [KO:K04200]
101716110  Mrap; melanocortin 2 receptor accessory protein [KO:K22398]
101716905  Gnas; GNAS complex locus [KO:K04632]
101705689  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
101711366  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101718304  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101713887  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101719464  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
101702436  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101698189  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101712483  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101698293  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101714605  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101712263  Pde8b; phosphodiesterase 8B [KO:K18437] [EC:3.1.4.53]
101697131  Pde8a; phosphodiesterase 8A [KO:K18437] [EC:3.1.4.53]
101707235  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101721558  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101720551  Nr0b1; nuclear receptor subfamily 0 group B member 1 [KO:K08562]
101719136  Nr5a1; nuclear receptor subfamily 5 group A member 1 [KO:K08560]
101707788  Nr4a1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
101697506  Sp1; Sp1 transcription factor [KO:K04684]
101714961  Pbx1; PBX homeobox 1 [KO:K09355]
101712503  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
101717365  Atf2; activating transcription factor 2 [KO:K04450]
101724287  Atf4; activating transcription factor 4 [KO:K04374]
101715715  Creb3l2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
101698748  Creb3l1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
101716023  Creb3l3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
101706643  Creb3l4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
101718447  Creb3; cAMP responsive element binding protein 3 [KO:K09048]
101703315  Creb5; cAMP responsive element binding protein 5 [KO:K09047]
101715793  Atf6b; activating transcription factor 6 beta [KO:K09049]
101701311  cytochrome P450 11B1, mitochondrial [KO:K00497] [EC:1.14.15.4]
101726496  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
101708935  Star; steroidogenic acute regulatory protein [KO:K16931]
101703160  Nceh1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
101717217  Agt; angiotensinogen [KO:K09821]
101714068  Agtr1; angiotensin II receptor type 1 [KO:K04166]
101715420  Gnaq; G protein subunit alpha q [KO:K04634]
101722520  Gna11; G protein subunit alpha 11 [KO:K04635]
101725860  Plcb1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101696454  Plcb4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101697744  Plcb3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
101708380  Plcb2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101706047  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101716022  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101706978  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101722094  Kcnk2; potassium two pore domain channel subfamily K member 2 [KO:K04913]
101709921  Cacna1g; calcium voltage-gated channel subunit alpha1 G [KO:K04854]
101712631  Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
101723335  Cacna1i; calcium voltage-gated channel subunit alpha1 I [KO:K04856]
101717129  Cacna1c; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
101714832  Cacna1d; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
101722090  Cacna1f; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
101726232  Cacna1s; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
101699660  Orai1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
101706863  Kcna4; potassium voltage-gated channel subfamily A member 4 [KO:K04877]
101699991  Kcnk3; potassium two pore domain channel subfamily K member 3 [KO:K04914]
101703463  Ldlr; low density lipoprotein receptor [KO:K12473]
101703927  Scarb1; scavenger receptor class B member 1 [KO:K13885]
101704598  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
101707858  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
101707488  Hsd3b1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
101717066  steroid 21-hydroxylase [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
hgl00140  Steroid hormone biosynthesis
hgl04020  Calcium signaling pathway
hgl04024  cAMP signaling pathway
hgl04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04927   
LinkDB

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