KEGG   PATHWAY: ko04913
Entry
ko04913                     Pathway                                
Name
Ovarian steroidogenesis
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
ko04913  Ovarian steroidogenesis
ko04913

Other DBs
GO: 0050810
Orthology
K00044  HSD17B1; 17beta-estradiol 17-dehydrogenase [EC:1.1.1.62]
K00070  HSD3B; 3beta-hydroxy-Delta5-steroid dehydrogenase / steroid Delta-isomerase [EC:1.1.1.145 5.3.3.1]
K00461  ALOX5; arachidonate 5-lipoxygenase [EC:1.13.11.34]
K00498  CYP11A; cholesterol monooxygenase (side-chain-cleaving) [EC:1.14.15.6]
K00512  CYP17A; steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase [EC:1.14.14.19 1.14.14.32]
K01068  ACOT1_2_4; acyl-coenzyme A thioesterase 1/2/4 [EC:3.1.2.2]
K04119  AKR1C3; aldo-keto reductase family 1 member C3 [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
K04247  FSHR; follicle stimulating hormone receptor
K04248  LHCGR; lutropin-choriogonadotropic hormone receptor
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04526  INS; insulin
K04527  INSR, CD220; insulin receptor [EC:2.7.10.1]
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05250  FSHB; follitropin subunit beta
K05459  IGF1; insulin-like growth factor 1
K05498  BMP15, GDF9B; bone morphogenetic protein 15
K07408  CYP1A1; cytochrome P450 family 1 subfamily A1 [EC:1.14.14.1]
K07410  CYP1B1; cytochrome P450 family 1 subfamily B1 [EC:1.14.14.1]
K07418  CYP2J; cytochrome P450 family 2 subfamily J [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
K07434  CYP19A; aromatase [EC:1.14.14.14]
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08521  LHB; lutropin subunit beta
K08522  CGA; glycoprotein hormones alpha chain
K11987  PTGS2, COX2; prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K12473  LDLR; low-density lipoprotein receptor
K13368  HSD17B2; 17beta-estradiol 17-dehydrogenase / 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) [EC:1.1.1.62 1.1.1.239]
K13373  HSD17B7; 17beta-estradiol 17-dehydrogenase / 3beta-hydroxysteroid 3-dehydrogenase [EC:1.1.1.62 1.1.1.270]
K13885  SCARB1; scavenger receptor class B, member 1
K16342  PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]
K16620  BMP6; bone morphogenetic protein 6
K16931  STAR; steroidogenic acute regulatory protein, mitochondrial
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
ko00140  Steroid hormone biosynthesis
ko04350  TGF-beta signaling pathway
ko04910  Insulin signaling pathway
ko04912  GnRH signaling pathway

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