KEGG   PATHWAY: oor04913
Entry
oor04913                    Pathway                                
Name
Ovarian steroidogenesis - Orcinus orca (killer whale)
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
oor04913  Ovarian steroidogenesis
oor04913

Other DBs
GO: 0050810
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101271158  CGA; glycoprotein hormones alpha chain [KO:K08522]
101283991  LHB; lutropin subunit beta [KO:K08521]
101290430  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
101286834  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
101282939  neuroendocrine secretory protein 55-like [KO:K04632]
101278368  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101286207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101283651  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101289858  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101283178  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101273023  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101273592  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101273171  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101281654  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101269805  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101270052  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
101286206  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
101270543  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
117195357  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
101276207  acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]
101276466  ACOT4; peroxisomal succinyl-coenzyme A thioesterase isoform X1 [KO:K01068] [EC:3.1.2.2]
101283796  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
101287985  cytochrome P450 2J2 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101270299  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
101278494  INS; insulin [KO:K04526]
101283355  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
101269950  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
101281976  IGF1R; insulin-like growth factor 1 receptor isoform X4 [KO:K05087] [EC:2.7.10.1]
101283356  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
101286813  SCARB1; scavenger receptor class B member 1 isoform X2 [KO:K13885]
101277651  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
101284598  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
101283719  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
101283453  HSD17B1; 17-beta-hydroxysteroid dehydrogenase type 1 [KO:K00044] [EC:1.1.1.62]
101284697  HSD17B2; 17-beta-hydroxysteroid dehydrogenase type 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
101281536  aldo-keto reductase family 1 member C3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101273575  dihydrodiol dehydrogenase 3 isoform X7 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101286750  HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
101284283  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
101284624  FSHB; follitropin subunit beta [KO:K05250]
101290010  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
101283540  aromatase [KO:K07434] [EC:1.14.14.14]
101270659  aromatase-like [KO:K07434] [EC:1.14.14.14]
101289532  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
101287158  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
101278021  BMP15; bone morphogenetic protein 15 [KO:K05498]
101284701  BMP6; bone morphogenetic protein 6 [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
oor00140  Steroid hormone biosynthesis
oor04350  TGF-beta signaling pathway
oor04910  Insulin signaling pathway
oor04912  GnRH signaling pathway
KO pathway
ko04913   
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