KEGG   PATHWAY: uar04913
Entry
uar04913                    Pathway                                
Name
Ovarian steroidogenesis - Ursus americanus (American black bear)
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
uar04913  Ovarian steroidogenesis
uar04913

Other DBs
GO: 0050810
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123776172  CGA; glycoprotein hormones alpha chain [KO:K08522]
123776350  LHB; lutropin subunit beta [KO:K08521]
123785918  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
123803297  neuroendocrine secretory protein 55 [KO:K04632]
123803290  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
123789481  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123791264  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
123799951  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123795737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123802178  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
123794794  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123798393  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123801897  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123783548  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123801768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123795272  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123801377  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
123803827  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
123803837  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
123775802  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
123776483  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
123799005  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
123799009  acyl-coenzyme A thioesterase 1 isoform X1 [KO:K01068] [EC:3.1.2.2]
123800343  ALOX5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
123795371  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
123801412  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
123775502  INS; insulin [KO:K04526]
123777569  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
123780774  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
123790797  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
123777712  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
123780199  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
123780378  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
123790690  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
123795915  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
123781896  HSD17B1; 17-beta-hydroxysteroid dehydrogenase type 1 isoform X1 [KO:K00044] [EC:1.1.1.62]
123791352  HSD17B2; 17-beta-hydroxysteroid dehydrogenase type 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
123802294  AKR1C8; putative aldo-keto reductase family 1 member C8 isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
123800151  HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
123795008  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
123799532  follitropin subunit beta [KO:K05250]
123786108  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
123801876  aromatase [KO:K07434] [EC:1.14.14.14]
123799824  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
123790682  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
123796407  BMP15; bone morphogenetic protein 15 [KO:K05498]
123801596  BMP6; LOW QUALITY PROTEIN: 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
PMID:15541573
  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
PMID:15831519
  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
PMID:20937107
  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
PMID:11704115
  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
PMID:11883103
  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
PMID:16603089
  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
PMID:21862696
  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
PMID:20628033
  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
PMID:18440223
  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
PMID:11408113
  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
PMID:10630400
  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
PMID:17003287
  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
PMID:17008391
  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
PMID:11447221
  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
PMID:14769828
  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
PMID:16414178
  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
uar00140  Steroid hormone biosynthesis
uar04350  TGF-beta signaling pathway
uar04910  Insulin signaling pathway
uar04912  GnRH signaling pathway
KO pathway
ko04913   
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