KEGG   PATHWAY: mna04913
Entry
mna04913                    Pathway                                

Name
Ovarian steroidogenesis - Miniopterus natalensis
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
mna04913  Ovarian steroidogenesis
mna04913

Other DBs
GO: 0050810
Organism
Miniopterus natalensis [GN:mna]
Gene
107532807  CGA; glycoprotein hormones alpha chain [KO:K08522]
107531805  LHB; lutropin subunit beta [KO:K08521]
107544281  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107546298  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
107536544  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
107536549  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
107536550  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
107536561  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
107533453  ACOT4; acyl-coenzyme A thioesterase 4 [KO:K01068] [EC:3.1.2.2]
107533473  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
107533476  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
107527950  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
107531748  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
107546245  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
107540632  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
107545147  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
107527774  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
107533280  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
107529684  SCARB1; scavenger receptor class B member 1 [KO:K13885]
107535187  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
107535212  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
107542528  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
107528936  HSD17B1; estradiol 17-beta-dehydrogenase 1 isoform X1 [KO:K00044] [EC:1.1.1.62]
107525681  HSD17B2; estradiol 17-beta-dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
107542430  prostaglandin F synthase 1-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
107542432  prostaglandin-E(2) 9-reductase-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
107535110  HSD17B7; 3-keto-steroid reductase isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
107545288  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
107531918  FSHB; follitropin subunit beta [KO:K05250]
107544288  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
107546547  aromatase [KO:K07434] [EC:1.14.14.14]
107541766  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
107535216  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
107541458  BMP15; bone morphogenetic protein 15 [KO:K05498]
107529113  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-Hydroxyestradiol-17beta
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
mna00140  Steroid hormone biosynthesis
mna04350  TGF-beta signaling pathway
mna04910  Insulin signaling pathway
mna04912  GnRH signaling pathway
KO pathway
ko04913   
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