KEGG   PATHWAY: ccad04913
Entry
ccad04913                   Pathway                                
Name
Ovarian steroidogenesis - Cervus canadensis (wapiti)
Description
The ovarian steroids, 17-beta estradiol (E2) and progesterone (P4), are critical for normal uterine function, establishment and maintenance of pregnancy, and mammary gland development. Furthermore, the local effects that are essential for normal ovarian physiology are dependent on the endocrine, paracrine, and autocrine actions of E2, P4, and androgens. In most mammals (including humans and mice), ovarian steroidogenesis occurs according to the two-cell/two-gonadotropin theory. This theory describes how granulosa and theca cells work together to make the ovarian steroids. Theca cells respond to LH signaling by increasing the expression of enzymes necessary for the conversion of cholesterol to androgens, such as androstenedione (A) and testosterone (T). Granulosa cells respond to FSH signaling by increasing the expression of enzymes necessary for the conversion of theca-derived androgens into estrogens (E2 and estrone).
Class
Organismal Systems; Endocrine system
Pathway map
ccad04913  Ovarian steroidogenesis
ccad04913

Other DBs
GO: 0050810
Organism
Cervus canadensis (wapiti) [GN:ccad]
Gene
122422505  CGA; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
122420964  lutropin subunit beta isoform X1 [KO:K08521]
122441659  LHCGR; lutropin-choriogonadotropic hormone receptor isoform X1 [KO:K04248]
122448612  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
122448614  neuroendocrine secretory protein 55 [KO:K04632]
122454307  uncharacterized protein LOC122454307 [KO:K04632]
122438514  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
122454210  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
122441999  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
122443147  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
122444643  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
122427399  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
122421548  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
122451315  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
122432769  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
122440547  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
122436774  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
122452049  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
122443430  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
122443435  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
122444120  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
122444121  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
122443831  acyl-coenzyme A thioesterase 1-like isoform X1 [KO:K01068] [EC:3.1.2.2]
122443835  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
122443832  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
122443833  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
122443834  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
122446293  ALOX5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
122436913  cytochrome P450 2J2-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
122436914  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
122436915  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
122436916  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
122452326  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
122430981  INS; insulin [KO:K04526]
122440366  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
122423293  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
122454848  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
122440398  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
122424577  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
122432483  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
122455135  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
122445953  steroid 17-alpha-hydroxylase/17,20 lyase-like isoform X1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
122446740  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
122441588  HSD17B1; 17-beta-hydroxysteroid dehydrogenase type 1 isoform X1 [KO:K00044] [EC:1.1.1.62]
122421656  HSD17B2; 17-beta-hydroxysteroid dehydrogenase type 2 isoform X1 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
122448511  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122448512  prostaglandin F synthase 1-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122447956  dihydrodiol dehydrogenase 3-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122447959  dihydrodiol dehydrogenase 3 isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122447958  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122448455  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122448456  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122448454  prostaglandin F synthase 1-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122448269  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
122432561  3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7-like isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
122429981  HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
122435367  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
122449872  follitropin subunit beta-like [KO:K05250]
122449873  follitropin subunit beta [KO:K05250]
122441661  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
122443608  aromatase [KO:K07434] [EC:1.14.14.14]
122441577  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
122419730  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
122435399  BMP15; bone morphogenetic protein 15 [KO:K05498]
122429664  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
Compound
C00187  Cholesterol
C00219  Arachidonate
C00280  Androstenedione
C00410  Progesterone
C00468  Estrone
C00535  Testosterone
C00575  3',5'-Cyclic AMP
C00639  Prostaglandin F2alpha
C00951  Estradiol-17beta
C01176  17alpha-Hydroxyprogesterone
C01227  Dehydroepiandrosterone
C01953  Pregnenolone
C02249  Arachidonyl-CoA
C02530  Cholesterol ester
C04295  Androstenediol
C05138  17alpha-Hydroxypregnenolone
C05301  2-Hydroxyestradiol
C05356  5(S)-HPETE
C05966  15(S)-HPETE
C14209  4-Hydroxy-17beta-estradiol
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14777  12(S)-HETE
Reference
  Authors
Havelock JC, Rainey WE, Carr BR
  Title
Ovarian granulosa cell lines.
  Journal
Mol Cell Endocrinol 228:67-78 (2004)
DOI:10.1016/j.mce.2004.04.018
Reference
  Authors
Stocco DM, Wang X, Jo Y, Manna PR
  Title
Multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression: more complicated than we thought.
  Journal
Mol Endocrinol 19:2647-59 (2005)
DOI:10.1210/me.2004-0532
Reference
  Authors
Wen X, Li D, Tozer AJ, Docherty SM, Iles RK
  Title
Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles.
  Journal
Reprod Biol Endocrinol 8:117 (2010)
DOI:10.1186/1477-7827-8-117
Reference
  Authors
Erickson GF, Shimasaki S
  Title
The physiology of folliculogenesis: the role of novel growth factors.
  Journal
Fertil Steril 76:943-9 (2001)
DOI:10.1016/S0015-0282(01)02859-X
Reference
  Authors
Wood JR, Strauss JF 3rd
  Title
Multiple signal transduction pathways regulate ovarian steroidogenesis.
  Journal
Rev Endocr Metab Disord 3:33-46 (2002)
DOI:10.1023/A:1012748718150
Reference
  Authors
Drummond AE
  Title
The role of steroids in follicular growth.
  Journal
Reprod Biol Endocrinol 4:16 (2006)
DOI:10.1186/1477-7827-4-16
Reference
  Authors
Craig ZR, Wang W, Flaws JA
  Title
Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling.
  Journal
Reproduction 142:633-46 (2011)
DOI:10.1530/REP-11-0136
Reference
  Authors
Young JM, McNeilly AS
  Title
Theca: the forgotten cell of the ovarian follicle.
  Journal
Reproduction 140:489-504 (2010)
DOI:10.1530/REP-10-0094
Reference
  Authors
Diamanti-Kandarakis E, Argyrakopoulou G, Economou F, Kandaraki E, Koutsilieris M
  Title
Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS).
  Journal
J Steroid Biochem Mol Biol 109:242-6 (2008)
DOI:10.1016/j.jsbmb.2008.03.014
Reference
  Authors
Spicer LJ
  Title
Receptors for insulin-like growth factor-I and tumor necrosis factor-alpha are hormonally regulated in bovine granulosa and thecal cells.
  Journal
Anim Reprod Sci 67:45-58 (2001)
DOI:10.1016/S0378-4320(01)00114-2
Reference
  Authors
Wang X, Stocco DM
  Title
Cyclic AMP and arachidonic acid: a tale of two pathways.
  Journal
Mol Cell Endocrinol 158:7-12 (1999)
DOI:10.1016/S0303-7207(99)00130-6
Reference
  Authors
Wang X, Shen CL, Dyson MT, Yin X, Schiffer RB, Grammas P, Stocco DM
  Title
The involvement of epoxygenase metabolites of arachidonic acid in cAMP-stimulated steroidogenesis and steroidogenic acute regulatory protein gene expression.
  Journal
J Endocrinol 190:871-8 (2006)
DOI:10.1677/joe.1.06933
Reference
  Authors
Miyoshi T, Otsuka F, Inagaki K, Otani H, Takeda M, Suzuki J, Goto J, Ogura T, Makino H
  Title
Differential regulation of steroidogenesis by bone morphogenetic proteins in granulosa cells: involvement of extracellularly regulated kinase signaling and oocyte actions in follicle-stimulating hormone-induced estrogen production.
  Journal
Endocrinology 148:337-45 (2007)
DOI:10.1210/en.2006-0966
Reference
  Authors
Otsuka F, Moore RK, Shimasaki S
  Title
Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary.
  Journal
J Biol Chem 276:32889-95 (2001)
DOI:10.1074/jbc.M103212200
Reference
  Authors
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
  Title
The bone morphogenetic protein system in mammalian reproduction.
  Journal
Endocr Rev 25:72-101 (2004)
DOI:10.1210/er.2003-0007
Reference
  Authors
Lukacik P, Kavanagh KL, Oppermann U
  Title
Structure and function of human 17beta-hydroxysteroid dehydrogenases.
  Journal
Mol Cell Endocrinol 248:61-71 (2006)
DOI:10.1016/j.mce.2005.12.007
Related
pathway
ccad00140  Steroid hormone biosynthesis
ccad04350  TGF-beta signaling pathway
ccad04910  Insulin signaling pathway
ccad04912  GnRH signaling pathway
KO pathway
ko04913   
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