KEGG   PATHWAY: ccan04913
Entry
ccan04913                   Pathway                                
Name
Ovarian steroidogenesis - Castor canadensis (American beaver)
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
ccan04913  Ovarian steroidogenesis
ccan04913

Other DBs
GO: 0050810
Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109675369  Cga; glycoprotein hormones alpha chain [KO:K08522]
109682662  Lhb; LOW QUALITY PROTEIN: lutropin subunit beta [KO:K08521]
109678625  Lhcgr; lutropin-choriogonadotropic hormone receptor [KO:K04248]
109692784  Gnas; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
109692786  neuroendocrine secretory protein 55-like [KO:K04632]
109694874  Adcy1; LOW QUALITY PROTEIN: adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109695818  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
109685686  Adcy3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
109685852  Adcy4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
109701078  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109686365  Adcy6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
109698373  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
109678665  Adcy8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
109681681  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
109681696  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109688706  cAMP-dependent protein kinase catalytic subunit beta-like [KO:K04345] [EC:2.7.11.11]
109681298  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109688701  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109678488  Pla2g4d; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
109693126  Pla2g4e; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
109697572  cytosolic phospholipase A2 gamma-like isoform X1 [KO:K16342] [EC:3.1.1.4]
109697577  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
109697580  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
109697581  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
109682660  Pla2g4f; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
109685136  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
109688392  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
109688393  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
109688395  acyl-coenzyme A thioesterase 4-like [KO:K01068] [EC:3.1.2.2]
109691363  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
109691364  acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]
109700324  Alox5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
109684284  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
109685138  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
109689794  insulin [KO:K04526]
109694006  Insr; LOW QUALITY PROTEIN: insulin receptor [KO:K04527] [EC:2.7.10.1]
109677734  insulin-like growth factor I [KO:K05459]
109697466  Igf1; insulin-like growth factor I [KO:K05459]
109687530  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
109692527  Ldlr; LOW QUALITY PROTEIN: low-density lipoprotein receptor [KO:K12473]
109700549  Scarb1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
109679870  LOW QUALITY PROTEIN: steroidogenic acute regulatory protein, mitochondrial-like [KO:K16931]
109688944  Star; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
109687652  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
109691327  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
109687306  Hsd17b1; estradiol 17-beta-dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
109680174  LOW QUALITY PROTEIN: estradiol 17-beta-dehydrogenase 2-like [KO:K13368] [EC:1.1.1.62 1.1.1.239]
109678869  aldo-keto reductase family 1 member C1 homolog isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
109680334  prostaglandin-E(2) 9-reductase-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
109680990  prostaglandin F synthase 1-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
109690973  Hsd17b7; 3-keto-steroid reductase [KO:K13373] [EC:1.1.1.62 1.1.1.270]
109702728  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]
109702729  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
109701465  Fshb; follitropin subunit beta [KO:K05250]
109678035  Fshr; LOW QUALITY PROTEIN: follicle-stimulating hormone receptor [KO:K04247]
109679172  aromatase [KO:K07434] [EC:1.14.14.14]
109675669  aromatase-like [KO:K07434] [EC:1.14.14.14]
109685237  LOW QUALITY PROTEIN: cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
109701505  cytochrome P450 1A1-like [KO:K07408] [EC:1.14.14.1]
109675709  Bmp15; LOW QUALITY PROTEIN: bone morphogenetic protein 15 [KO:K05498]
109692215  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
ccan00140  Steroid hormone biosynthesis
ccan04350  TGF-beta signaling pathway
ccan04910  Insulin signaling pathway
ccan04912  GnRH signaling pathway
KO pathway
ko04913   
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