KEGG   PATHWAY: aamp04913
Entry
aamp04913                   Pathway                                
Name
Ovarian steroidogenesis - Arvicola amphibius (Eurasian water vole)
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
aamp04913  Ovarian steroidogenesis
aamp04913

Other DBs
GO: 0050810
Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119826871  Cga; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
119802941  Lhb; lutropin subunit beta [KO:K08521]
119808150  Lhcgr; lutropin-choriogonadotropic hormone receptor [KO:K04248]
119814107  Gnas; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
119814944  neuroendocrine secretory protein 55 isoform X1 [KO:K04632]
119800365  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
119809754  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
119807554  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
119800380  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
119824190  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
119822579  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
119801694  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
119823121  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
119811771  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
119800975  Prkacb; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
119802004  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
119827616  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
119815214  Pla2g4f; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
119815600  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
119815216  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
119820365  cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
119814209  cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
119818512  acyl-coenzyme A thioesterase 5-like [KO:K01068] [EC:3.1.2.2]
119818544  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
119818547  peroxisomal succinyl-coenzyme A thioesterase isoform X1 [KO:K01068] [EC:3.1.2.2]
119818549  acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]
119818582  LOW QUALITY PROTEIN: acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
119818584  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
119807525  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
119816658  cytochrome P450 2J3-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816659  cytochrome P450 2J3-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816660  cytochrome P450 2J4-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816661  cytochrome P450 2J4 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816663  cytochrome P450 2J4-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816664  cytochrome P450 2J3 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816666  cytochrome P450 2J4-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119816978  cytochrome P450 2J3-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
119827843  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
119805421  Ins; insulin [KO:K04526]
119825604  Insr; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
119803277  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
119802616  Igf1r; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
119809008  Ldlr; low-density lipoprotein receptor [KO:K12473]
119824480  Scarb1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
119811741  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
119809739  cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:1.14.15.6]
119802303  steroid 17-alpha-hydroxylase/17,20 lyase isoform X1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
119813404  Hsd17b1; 17-beta-hydroxysteroid dehydrogenase type 1 [KO:K00044] [EC:1.1.1.62]
119801690  Hsd17b2; 17-beta-hydroxysteroid dehydrogenase type 2 isoform X1 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
119816160  aldo-keto reductase family 1 member C15-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
119816243  aldo-keto reductase family 1 member C15 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
119826549  aldo-keto reductase family 1 member C15-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
119827319  Hsd17b7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
119801286  NADPH-dependent 3-keto-steroid reductase HSD3B3-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
119801287  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
119801288  NADPH-dependent 3-keto-steroid reductase HSD3B3-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
119801289  NADPH-dependent 3-keto-steroid reductase HSD3B3-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
119815747  Fshb; follitropin subunit beta [KO:K05250]
119807959  Fshr; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
119810788  aromatase [KO:K07434] [EC:1.14.14.14]
119807802  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
119808952  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
119804142  Bmp15; bone morphogenetic protein 15 [KO:K05498]
119816323  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
aamp00140  Steroid hormone biosynthesis
aamp04350  TGF-beta signaling pathway
aamp04910  Insulin signaling pathway
aamp04912  GnRH signaling pathway
KO pathway
ko04913   
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