KEGG   PATHWAY: mlf04913
Entry
mlf04913                    Pathway                                
Name
Ovarian steroidogenesis - Myotis lucifugus (little brown bat)
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
mlf04913  Ovarian steroidogenesis
mlf04913

Other DBs
GO: 0050810
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102427356  CGA; glycoprotein hormones alpha chain [KO:K08522]
102435177  LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]
102428502  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X11 [KO:K04632]
102433989  neuroendocrine secretory protein 55-like [KO:K04632]
102430354  ADCY2; adenylate cyclase type 2 isoform X2 [KO:K08042] [EC:4.6.1.1]
102442682  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102417969  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
102425254  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102433159  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102423495  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102422477  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
102437773  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102417960  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102422494  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102424085  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102419721  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
102420552  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102422798  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102440418  acyl-coenzyme A thioesterase 1 isoform X1 [KO:K01068] [EC:3.1.2.2]
102441032  ACOT4; acyl-coenzyme A thioesterase 4 [KO:K01068] [EC:3.1.2.2]
102418693  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
102439141  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
102423775  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
102430737  INS; insulin [KO:K04526]
102437355  INSR; LOW QUALITY PROTEIN: insulin receptor [KO:K04527] [EC:2.7.10.1]
102424041  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
102430595  IGF1R; LOW QUALITY PROTEIN: insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102432506  LDLR; LOW QUALITY PROTEIN: low-density lipoprotein receptor [KO:K12473]
102428887  SCARB1; LOW QUALITY PROTEIN: scavenger receptor class B member 1 [KO:K13885]
102421639  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
102433032  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
102417518  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
102420780  HSD17B1; estradiol 17-beta-dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
102419373  HSD17B2; estradiol 17-beta-dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
102428982  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]
102421358  aldo-keto reductase family 1 member C1 homolog [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
102428751  HSD17B7; LOW QUALITY PROTEIN: 3-keto-steroid reductase [KO:K13373] [EC:1.1.1.62 1.1.1.270]
106694328  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
102443318  FSHB; follitropin subunit beta [KO:K05250]
102426759  FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]
102420943  aromatase [KO:K07434] [EC:1.14.14.14]
102417339  LOW QUALITY PROTEIN: cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
102437172  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
102423385  LOW QUALITY PROTEIN: bone morphogenetic protein 15-like [KO:K05498]
102438131  BMP15; bone morphogenetic protein 15 [KO:K05498]
102420612  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-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
mlf00140  Steroid hormone biosynthesis
mlf04350  TGF-beta signaling pathway
mlf04910  Insulin signaling pathway
mlf04912  GnRH signaling pathway
KO pathway
ko04913   
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