Entry |
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Name |
Cortisol synthesis and secretion - Homo sapiens (human)
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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).
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Class |
Organismal Systems; Endocrine system
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Pathway map |
hsa04927 | Cortisol synthesis and secretion |

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Network |
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Element |
N00297 | ACTH-cortisol signaling pathway |
N00306 | SF-1-mediated transcription |
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Disease |
H02316 | Adrenal insufficiency, NR5A1 related |
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Drug |
D00146 | Corticotropin (USP/INN) |
D02105 | Tetracosactide acetate (JAN) |
D03593 | Corticotropin zinc hydroxide |
D06544 | Corticotropin, repository (USP) |
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Other DBs |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
56246 | MRAP; melanocortin 2 receptor accessory protein [KO:K22398] |
190 | NR0B1; nuclear receptor subfamily 0 group B member 1 [KO:K08562] |
2516 | NR5A1; nuclear receptor subfamily 5 group A member 1 [KO:K08560] |
3164 | NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465] |
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] |
90993 | CREB3L1; cAMP responsive element binding protein 3 like 1 [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] |
148327 | CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048] |
9586 | CREB5; cAMP responsive element binding protein 5 [KO:K09047] |
1388 | ATF6B; activating transcription factor 6 beta [KO:K09049] |
6770 | STAR; steroidogenic acute regulatory protein [KO:K16931] |
57552 | NCEH1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-] |
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] |
3776 | KCNK2; potassium two pore domain channel subfamily K member 2 [KO:K04913] |
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] |
3739 | KCNA4; potassium voltage-gated channel subfamily A member 4 [KO:K04877] |
3777 | KCNK3; potassium two pore domain channel subfamily K member 3 [KO:K04914] |
3949 | LDLR; low density lipoprotein receptor [KO:K12473] |
949 | SCARB1; scavenger receptor class B member 1 [KO:K13885] |
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Compound |
C01176 | 17alpha-Hydroxyprogesterone |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
C05138 | 17alpha-Hydroxypregnenolone |
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Reference |
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Authors |
Gallo-Payet N, Battista MC |
Title |
Steroidogenesis-adrenal cell signal transduction. |
Journal |
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Reference |
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Authors |
Enyeart JJ |
Title |
Biochemical and Ionic signaling mechanisms for ACTH-stimulated cortisol production. |
Journal |
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Reference |
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Authors |
Bandulik S, Tauber P, Lalli E, Barhanin J, Warth R |
Title |
Two-pore domain potassium channels in the adrenal cortex. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Shen WJ, Azhar S, Kraemer FB |
Title |
ACTH Regulation of Adrenal SR-B1. |
Journal |
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Reference |
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Authors |
Ruggiero C, Lalli E |
Title |
Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes. |
Journal |
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Reference |
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Authors |
Margioris AN, Tsatsanis C |
Title |
ACTH Action on the Adrenals |
Journal |
Endotext (2000) |
Reference |
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Authors |
Spiga F, Lightman SL |
Title |
Dynamics of adrenal glucocorticoid steroidogenesis in health and disease. |
Journal |
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Reference |
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Authors |
Tsai LC, Beavo JA |
Title |
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. |
Journal |
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Reference |
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Authors |
Odermatt A, Strajhar P, Engeli RT |
Title |
Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools. |
Journal |
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Reference |
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Authors |
Manna PR, Stetson CL, Slominski AT, Pruitt K |
Title |
Role of the steroidogenic acute regulatory protein in health and disease. |
Journal |
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Reference |
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Authors |
Jackson DS, Ramachandrappa S, Clark AJ, Chan LF |
Title |
Melanocortin receptor accessory proteins in adrenal disease and obesity. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Midzak A, Papadopoulos V |
Title |
Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies. |
Journal |
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Reference |
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Authors |
Calebiro D, Di Dalmazi G, Bathon K, Ronchi CL, Beuschlein F |
Title |
cAMP signaling in cortisol-producing adrenal adenoma. |
Journal |
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Reference |
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Authors |
Turcu AF, Auchus RJ |
Title |
Adrenal steroidogenesis and congenital adrenal hyperplasia. |
Journal |
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Related pathway |
hsa04960 | Aldosterone-regulated sodium reabsorption |
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KO pathway |
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LinkDB |
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