KEGG   PATHWAY: ncar04913
Entry
ncar04913                   Pathway                                
Name
Ovarian steroidogenesis - Sciurus carolinensis (gray squirrel)
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
ncar04913  Ovarian steroidogenesis
ncar04913

Other DBs
GO: 0050810
Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124989487  glycoprotein hormones alpha chain isoform X1 [KO:K08522]
124967103  lutropin subunit beta [KO:K08521]
124963615  lutropin-choriogonadotropic hormone receptor [KO:K04248]
124978161  neuroendocrine secretory protein 55 [KO:K04632]
124975134  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124990345  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
124987010  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124962927  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
124978229  LOW QUALITY PROTEIN: adenylate cyclase type 4-like [KO:K08044] [EC:4.6.1.1]
124992559  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
124983776  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
124966834  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
124965096  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
124970113  LOW QUALITY PROTEIN: adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
124985819  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124969119  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124976716  cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
124976990  cytosolic phospholipase A2 zeta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
124978216  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
124978217  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
124962073  cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
124974890  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
124978285  acyl-coenzyme A thioesterase 1-like [KO:K01068] [EC:3.1.2.2]
124976632  peroxisomal succinyl-coenzyme A thioesterase-like [KO:K01068] [EC:3.1.2.2]
124985624  polyunsaturated fatty acid 5-lipoxygenase-like [KO:K00461] [EC:1.13.11.34]
124985161  LOW QUALITY PROTEIN: polyunsaturated fatty acid 5-lipoxygenase-like [KO:K00461] [EC:1.13.11.34]
124985243  LOW QUALITY PROTEIN: polyunsaturated fatty acid 5-lipoxygenase-like [KO:K00461] [EC:1.13.11.34]
124975507  LOW QUALITY PROTEIN: polyunsaturated fatty acid 5-lipoxygenase-like [KO:K00461] [EC:1.13.11.34]
124966849  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
124962420  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
124960685  insulin [KO:K04526]
124968393  insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
124983128  insulin-like growth factor I isoform X1 [KO:K05459]
124978062  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
124968885  low-density lipoprotein receptor-like [KO:K12473]
124990716  scavenger receptor class B member 1 isoform X1 [KO:K13885]
124983155  steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
124977503  cholesterol side-chain cleavage enzyme, mitochondrial-like isoform X1 [KO:K00498] [EC:1.14.15.6]
124985398  steroid 17-alpha-hydroxylase/17,20 lyase-like [KO:K00512] [EC:1.14.14.19 1.14.14.32]
124967024  estradiol 17-beta-dehydrogenase 2-like [KO:K13368] [EC:1.1.1.62 1.1.1.239]
124961142  aldo-keto reductase family 1 member C3-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
124961655  aldo-keto reductase family 1 member C3-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
124990069  3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
124992819  LOW QUALITY PROTEIN: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124990189  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124964015  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
124960440  follitropin subunit beta [KO:K05250]
124963360  follicle-stimulating hormone receptor isoform X1 [KO:K04247]
124977775  aromatase [KO:K07434] [EC:1.14.14.14]
124962692  cytochrome P450 1B1 isoform X1 [KO:K07410] [EC:1.14.14.1]
124977051  cytochrome P450 1A1-like [KO:K07408] [EC:1.14.14.1]
124975310  bone morphogenetic protein 15-like [KO:K05498]
124988517  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
ncar00140  Steroid hormone biosynthesis
ncar04350  TGF-beta signaling pathway
ncar04910  Insulin signaling pathway
ncar04912  GnRH signaling pathway
KO pathway
ko04913   
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