KEGG   PATHWAY: pon04913
Entry
pon04913                    Pathway                                
Name
Ovarian steroidogenesis - Pongo abelii (Sumatran orangutan)
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
pon04913  Ovarian steroidogenesis
pon04913

Other DBs
GO: 0050810
Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100462106  CGA; glycoprotein hormones alpha chain isoform X2 [KO:K08522]
100454280  LHB; lutropin subunit beta [KO:K08521]
100457164  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
100442753  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X3 [KO:K04632]
103888841  neuroendocrine secretory protein 55 [KO:K04632]
100449504  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
100445431  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100431221  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
100460806  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100454138  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100438178  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100436577  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
100461383  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
103889530  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100174748  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform 2 [KO:K04345] [EC:2.7.11.11]
100431906  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
100437102  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100454614  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100173125  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100447631  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
100434495  PLA2G4C; cytosolic phospholipase A2 gamma isoform X3 [KO:K16342] [EC:3.1.1.4]
100454977  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100448616  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
100443692  ACOT4; acyl-coenzyme A thioesterase 4 [KO:K01068] [EC:3.1.2.2]
100442699  acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]
100444412  ACOT2; acyl-coenzyme A thioesterase 2, mitochondrial [KO:K01068] [EC:3.1.2.2]
100460538  ALOX5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
100447634  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100436566  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100451422  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
100444645  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100172156  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100447659  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
100459938  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
100455906  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
100433169  cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:1.14.15.6]
100439753  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
100456666  LOW QUALITY PROTEIN: estradiol 17-beta-dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
100458375  estradiol 17-beta-dehydrogenase 1-like isoform X1 [KO:K00044] [EC:1.1.1.62]
112129590  estradiol 17-beta-dehydrogenase 1-like [KO:K00044] [EC:1.1.1.62]
100456547  HSD17B2; estradiol 17-beta-dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
100174617  AKR1C3; aldo-keto reductase family 1 member C3 homolog [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
100462259  aldo-keto reductase family 1 member C1 homolog [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
100432652  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]
100461633  prostaglandin F synthase 1-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
100446761  HSD17B7; 3-keto-steroid reductase isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
100451655  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100452394  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100450898  LOW QUALITY PROTEIN: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100444274  FSHB; follitropin subunit beta [KO:K05250]
100455725  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
100439777  aromatase [KO:K07434] [EC:1.14.14.14]
100172192  CYP1B1; cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
100457153  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
100441790  BMP15; bone morphogenetic protein 15 [KO:K05498]
100445825  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
pon00140  Steroid hormone biosynthesis
pon04350  TGF-beta signaling pathway
pon04910  Insulin signaling pathway
pon04912  GnRH signaling pathway
KO pathway
ko04913   
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