KEGG   PATHWAY: oas04913
Entry
oas04913                    Pathway                                
Name
Ovarian steroidogenesis - Ovis aries (sheep)
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
oas04913  Ovarian steroidogenesis
oas04913

Other DBs
GO: 0050810
Organism
Ovis aries (sheep) [GN:oas]
Gene
443538  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
443395  LHB; lutropin subunit beta precursor [KO:K08521]
101113228  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
101115640  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X5 [KO:K04632]
101102411  neuroendocrine secretory protein 55 [KO:K04632]
101117327  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101102089  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101108203  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101119139  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105602258  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101105735  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101112667  ADCY7; adenylate cyclase type 7 isoform X7 [KO:K08047] [EC:4.6.1.1]
101121944  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101122401  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
443094  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101108785  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101111472  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101115372  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
101115878  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X2 [KO:K16342] [EC:3.1.1.4]
101116150  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
101116403  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
101104407  acyl-coenzyme A thioesterase 1-like isoform X1 [KO:K01068] [EC:3.1.2.2]
106990150  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
101103726  peroxisomal succinyl-coenzyme A thioesterase isoform X1 [KO:K01068] [EC:3.1.2.2]
101104669  LOW QUALITY PROTEIN: acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
101117390  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X2 [KO:K00461] [EC:1.13.11.34]
101121563  cytochrome P450 2J2 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101121820  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]
768095  CYP2J; cytochrome P450, family 2, subfamily J [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
443460  PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
114110121  INS; insulin [KO:K04526]
443431  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
443318  IGF1; insulin-like growth factor I precursor [KO:K05459]
443515  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
443535  LDLR; low-density lipoprotein receptor isoform X2 [KO:K12473]
101115654  SCARB1; scavenger receptor class B member 1 isoform X5 [KO:K13885]
443122  STAR; steroidogenic acute regulatory protein, mitochondrial precursor [KO:K16931]
100048994  CYP11A1; cholesterol side-chain cleavage enzyme, mitochondrial precursor [KO:K00498] [EC:1.14.15.6]
105601846  CYP17; steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
493968  CYP17A1; steroid 17-alpha-hydroxylase/17,20 lyase precursor [KO:K00512] [EC:1.14.14.19 1.14.14.32]
101110778  HSD17B1; 17-beta-hydroxysteroid dehydrogenase type 1 [KO:K00044] [EC:1.1.1.62]
100913161  HSD17B2; 17-beta-hydroxysteroid dehydrogenase type 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
101107541  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]
106990122  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101109111  dihydrodiol dehydrogenase 3 isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101109377  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]
101110434  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]
101107119  dihydrodiol dehydrogenase 3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
105614315  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]
101110693  LOW QUALITY PROTEIN: prostaglandin F synthase 1-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
114108656  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]
101107809  dihydrodiol dehydrogenase 3-like isoform X3 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101110013  HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X3 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
100190978  HSD3B1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
443387  FSHB; follitropin subunit beta precursor [KO:K05250]
443299  FSHR; follicle-stimulating hormone receptor precursor [KO:K04247]
100144423  CYP19; aromatase [KO:K07434] [EC:1.14.14.14]
101119706  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
100170113  CYP1A1; cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
100141303  BMP15; bone morphogenetic protein 15 precursor [KO:K05498]
443174  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
oas00140  Steroid hormone biosynthesis
oas04350  TGF-beta signaling pathway
oas04910  Insulin signaling pathway
oas04912  GnRH signaling pathway
KO pathway
ko04913   
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