KEGG   PATHWAY: pdic04913
Entry
pdic04913                   Pathway                                
Name
Ovarian steroidogenesis - Phyllostomus discolor (pale spear-nosed bat)
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
pdic04913  Ovarian steroidogenesis
pdic04913

Other DBs
GO: 0050810
Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114495040  CGA; glycoprotein hormones alpha chain [KO:K08522]
114511641  lutropin subunit beta [KO:K08521]
114500728  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
114506244  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
114507035  neuroendocrine secretory protein 55-like [KO:K04632]
114490247  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114508056  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
114500049  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114492860  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114490544  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114512738  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
114488191  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
114514654  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114503776  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
114505902  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
114502442  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114496184  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114512046  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
114492224  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
114492506  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
114492507  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
114492921  PLA2G4B; cytosolic phospholipase A2 beta isoform X3 [KO:K16342] [EC:3.1.1.4]
114492151  LOW QUALITY PROTEIN: acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
114493134  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
118497488  acyl-coenzyme A amino acid N-acyltransferase 2-like [KO:K01068] [EC:3.1.2.2]
114496046  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
114496360  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
114496679  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
114497261  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
114497336  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]
114511915  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
114500824  INS; insulin [KO:K04526]
114509225  INSR; LOW QUALITY PROTEIN: insulin receptor [KO:K04527] [EC:2.7.10.1]
114513472  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
114488551  IGF1R; insulin-like growth factor 1 receptor isoform X2 [KO:K05087] [EC:2.7.10.1]
114503660  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
114509733  SCARB1; scavenger receptor class B member 1 isoform X2 [KO:K13885]
114508733  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
114492772  cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:1.14.15.6]
114497592  steroid 17-alpha-hydroxylase/17,20 lyase isoform X1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
114504219  HSD17B1; estradiol 17-beta-dehydrogenase 1 isoform X1 [KO:K00044] [EC:1.1.1.62]
114488332  HSD17B2; estradiol 17-beta-dehydrogenase 2 isoform X1 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
114492418  aldo-keto reductase family 1 member C1 homolog isoform X13 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
114511975  HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
114489256  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
114500606  FSHB; follitropin subunit beta [KO:K05250]
114500315  FSHR; follicle-stimulating hormone receptor [KO:K04247]
114493114  aromatase [KO:K07434] [EC:1.14.14.14]
114500131  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
114492343  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
114505435  BMP15; bone morphogenetic protein 15 [KO:K05498]
114497201  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
pdic00140  Steroid hormone biosynthesis
pdic04350  TGF-beta signaling pathway
pdic04910  Insulin signaling pathway
pdic04912  GnRH signaling pathway
KO pathway
ko04913   
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