KEGG   PATHWAY: mmma04913
Entry
mmma04913                   Pathway                                
Name
Ovarian steroidogenesis - Marmota marmota marmota (Alpine marmot)
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
mmma04913  Ovarian steroidogenesis
mmma04913

Other DBs
GO: 0050810
Organism
Marmota marmota marmota (Alpine marmot) [GN:mmma]
Gene
107152608  Cga; glycoprotein hormones alpha chain [KO:K08522]
107151713  Lhb; lutropin subunit beta [KO:K08521]
107137114  Lhcgr; lutropin-choriogonadotropic hormone receptor isoform X1 [KO:K04248]
107137583  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
107137572  Gnas; neuroendocrine secretory protein 55 [KO:K04632]
107146235  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
107146314  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
107137043  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
107147463  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
107143106  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
107148587  Adcy6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
107144878  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
107143016  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
107146665  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
107135580  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
107158295  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107144974  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107137643  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
107138189  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
107138195  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
107147293  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
107151580  Pla2g4c; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
107137645  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
107148947  LOW QUALITY PROTEIN: acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
107144493  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
107144481  acyl-coenzyme A thioesterase 1-like isoform X1 [KO:K01068] [EC:3.1.2.2]
107153379  Alox5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
107141706  cytochrome P450 2J2 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
107147540  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
107157066  Ins; insulin [KO:K04526]
107157473  Insr; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
107139962  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
107148359  Igf1r; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
107145197  Ldlr; low-density lipoprotein receptor isoform X2 [KO:K12473]
107156374  Scarb1; scavenger receptor class B member 1 [KO:K13885]
107155355  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
107137576  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
107149847  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
107150567  Hsd17b1; 17-beta-hydroxysteroid dehydrogenase type 1 [KO:K00044] [EC:1.1.1.62]
107150866  Hsd17b2; 17-beta-hydroxysteroid dehydrogenase type 2 isoform X2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
107147446  Hsd17b7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
107156205  Hao2; 2-Hydroxyacid oxidase 2 isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
107156207  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
107156209  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
107134387  Fshb; follitropin subunit beta [KO:K05250]
107137113  Fshr; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
107138103  LOW QUALITY PROTEIN: aromatase [KO:K07434] [EC:1.14.14.14]
107137344  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
107137939  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
107159275  bone morphogenetic protein 15-like [KO:K05498]
107160936  bone morphogenetic protein 15-like [KO:K05498]
107149378  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
mmma00140  Steroid hormone biosynthesis
mmma04350  TGF-beta signaling pathway
mmma04910  Insulin signaling pathway
mmma04912  GnRH signaling pathway
KO pathway
ko04913   
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