KEGG   PATHWAY: llv04913
Entry
llv04913                    Pathway                                
Name
Ovarian steroidogenesis - Lutra lutra (Eurasian river 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
llv04913  Ovarian steroidogenesis
llv04913

Other DBs
GO: 0050810
Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125103297  glycoprotein hormones alpha chain [KO:K08522]
125089666  lutropin subunit beta [KO:K08521]
125108531  lutropin-choriogonadotropic hormone receptor isoform X1 [KO:K04248]
125108178  neuroendocrine secretory protein 55 [KO:K04632]
125108177  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
125081029  adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
125099871  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
125108687  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125104720  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
125103305  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
125106490  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
125088705  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125098951  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
125091072  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
125083608  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
125097539  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125086218  cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
125104288  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
125104913  cytosolic phospholipase A2 delta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
125104914  cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
125105491  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
125085017  polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
125097704  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
125086360  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
125079072  insulin [KO:K04526]
125085453  insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
125106739  insulin-like growth factor I isoform X1 [KO:K05459]
125105350  insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
125084611  low-density lipoprotein receptor [KO:K12473]
125081851  scavenger receptor class B member 1 isoform X1 [KO:K13885]
125092751  steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
125105609  cholesterol side-chain cleavage enzyme, mitochondrial-like isoform X1 [KO:K00498] [EC:1.14.15.6]
125084794  steroid 17-alpha-hydroxylase/17,20 lyase isoform X1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
125087635  estradiol 17-beta-dehydrogenase 1-like isoform X1 [KO:K00044] [EC:1.1.1.62]
125089092  17-beta-hydroxysteroid dehydrogenase type 2-like [KO:K13368] [EC:1.1.1.62 1.1.1.239]
125107753  prostaglandin F synthase 1-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
125086086  LOW QUALITY PROTEIN: 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7-like [KO:K13373] [EC:1.1.1.62 1.1.1.270]
125099255  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:1.1.1.145 5.3.3.1]
125080146  follitropin subunit beta [KO:K05250]
125108913  LOW QUALITY PROTEIN: follicle-stimulating hormone receptor-like [KO:K04247]
125105151  aromatase [KO:K07434] [EC:1.14.14.14]
125109142  cytochrome P450 1B1-like [KO:K07410] [EC:1.14.14.1]
125105138  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
125092078  bone morphogenetic protein 15-like [KO:K05498]
125101749  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
llv00140  Steroid hormone biosynthesis
llv04350  TGF-beta signaling pathway
llv04910  Insulin signaling pathway
llv04912  GnRH signaling pathway
KO pathway
ko04913   
LinkDB

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