KEGG   PATHWAY: hgl04913
Entry
hgl04913                    Pathway                                
Name
Ovarian steroidogenesis - Heterocephalus glaber (naked mole-rat)
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
hgl04913  Ovarian steroidogenesis
hgl04913

Other DBs
GO: 0050810
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101704979  Cga; glycoprotein hormones, alpha polypeptide [KO:K08522]
101710917  Lhb; luteinizing hormone beta polypeptide [KO:K08521]
101719623  lutropin subunit beta [KO:K08521]
101718960  Lhcgr; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
101716905  Gnas; GNAS complex locus [KO:K04632]
101705689  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
101711366  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101718304  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101713887  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101719464  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
101702436  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101698189  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101712483  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101698293  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101714605  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101707235  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101721558  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101705849  Pla2g4e; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
101706202  Pla2g4f; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
101703792  Pla2g4b; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
101717491  Pla2g4d; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
101713091  Pla2g4c; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
101704061  Pla2g4a; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
101722826  acyl-coenzyme A thioesterase 3 [KO:K01068] [EC:3.1.2.2]
101700210  Alox5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
101719021  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101719368  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101704771  Ptgs2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
101719971  Ins; insulin [KO:K04526]
101722168  Insr; insulin receptor [KO:K04527] [EC:2.7.10.1]
101707684  Igf1; insulin like growth factor 1 [KO:K05459]
101710224  Igf1r; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
101703463  Ldlr; low density lipoprotein receptor [KO:K12473]
101703927  Scarb1; scavenger receptor class B member 1 [KO:K13885]
101708935  Star; steroidogenic acute regulatory protein [KO:K16931]
101704598  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
101726496  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
101720493  Hsd17b1; hydroxysteroid 17-beta dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
101719685  Hsd17b2; hydroxysteroid 17-beta dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
101702106  aldo-keto reductase family 1 member C23-like protein [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
101712707  Hsd17b7; hydroxysteroid 17-beta dehydrogenase 7 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
101707858  3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]
101707488  Hsd3b1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
101717666  Fshb; follicle stimulating hormone beta subunit [KO:K05250]
101719312  Fshr; follicle stimulating hormone receptor [KO:K04247]
101702005  aromatase [KO:K07434] [EC:1.14.14.14]
101701066  cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
101707509  cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
101697994  Bmp15; bone morphogenetic protein 15 [KO:K05498]
101707462  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
hgl00140  Steroid hormone biosynthesis
hgl04350  TGF-beta signaling pathway
hgl04910  Insulin signaling pathway
hgl04912  GnRH signaling pathway
KO pathway
ko04913   
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