KEGG   PATHWAY: elk04913
Entry
elk04913                    Pathway                                
Name
Ovarian steroidogenesis - Enhydra lutris kenyoni (northern sea otter)
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
elk04913  Ovarian steroidogenesis
elk04913

Other DBs
GO: 0050810
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111158799  glycoprotein hormones alpha chain [KO:K08522]
111160757  lutropin subunit beta [KO:K08521]
111148140  lutropin-choriogonadotropic hormone receptor [KO:K04248]
111141614  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
111141312  neuroendocrine secretory protein 55 [KO:K04632]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111150782  cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
111140157  LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
111162039  cytosolic phospholipase A2 beta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
111140619  cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
111160468  cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
111140503  acyl-coenzyme A thioesterase 4-like [KO:K01068] [EC:3.1.2.2]
111144974  arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
111143525  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
111150791  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
111150279  insulin [KO:K04526]
111161798  insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
111142293  insulin-like growth factor I [KO:K05459]
111142036  insulin-like growth factor I isoform X1 [KO:K05459]
111152643  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
111162438  low-density lipoprotein receptor [KO:K12473]
111156379  scavenger receptor class B member 1 isoform X1 [KO:K13885]
111144498  steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
111153362  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
111145221  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
111151543  estradiol 17-beta-dehydrogenase 1 isoform X1 [KO:K00044] [EC:1.1.1.62]
111152983  estradiol 17-beta-dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
111158636  prostaglandin F synthase 1-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
111151061  3-keto-steroid reductase isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
111143436  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
111150244  follitropin subunit beta [KO:K05250]
111148068  follicle-stimulating hormone receptor isoform X1 [KO:K04247]
111138628  aromatase isoform X1 [KO:K07434] [EC:1.14.14.14]
111158468  cytochrome P450 1B1-like [KO:K07410] [EC:1.14.14.1]
111158469  cytochrome P450 1B1-like [KO:K07410] [EC:1.14.14.1]
111153267  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
111150546  bone morphogenetic protein 15 [KO:K05498]
111156661  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
elk00140  Steroid hormone biosynthesis
elk04350  TGF-beta signaling pathway
elk04910  Insulin signaling pathway
elk04912  GnRH signaling pathway
KO pathway
ko04913   
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