KEGG   PATHWAY: hsa04913
Entry
hsa04913                    Pathway                                

Name
Ovarian steroidogenesis - Homo sapiens (human)
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
hsa04913  Ovarian steroidogenesis
hsa04913

Disease
H00599  46,XX gonadal dysgenesis
H00627  Premature ovarian failure
H01383  Hyperlipoproteinemia type IIa
H01973  Fertile eunuch syndrome
H02020  Aromatase deficiency
Drug
D02692  Menotropins (USAN)
D04429  Follitropin alfa (genetical recombination) (JAN)
D04430  Follitropin beta (genetical recombination) (JAN)
D04824  Lutropin alfa (USAN/INN)
D05258  Serum gonadotrophin (JAN)
D06269  Urofollitropin (USAN/INN)
D06400  Follitropin delta (genetical recombination) (JAN)
D06457  Gonadotropin, chorionic (USP)
D06459  Purified human menopausal gonadotrophin (JAN)
D08895  Corifollitropin alfa (INN/USAN)
Other DBs
GO: 0050810
Organism
Homo sapiens (human) [GN:hsa]
Gene
1081  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
3972  LHB; luteinizing hormone subunit beta [KO:K08521]
3973  LHCGR; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
2778  GNAS; GNAS complex locus [KO:K04632]
107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
123745  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
5321  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
8681  JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
100137049  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
8605  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
283748  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
255189  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
122970  ACOT4; acyl-CoA thioesterase 4 [KO:K01068] [EC:3.1.2.2]
10965  ACOT2; acyl-CoA thioesterase 2 [KO:K01068] [EC:3.1.2.2]
641371  ACOT1; acyl-CoA thioesterase 1 [KO:K01068] [EC:3.1.2.2]
240  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
1573  CYP2J2; cytochrome P450 family 2 subfamily J member 2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
5743  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
3630  INS; insulin [KO:K04526]
3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
3949  LDLR; low density lipoprotein receptor [KO:K12473]
949  SCARB1; scavenger receptor class B member 1 [KO:K13885]
6770  STAR; steroidogenic acute regulatory protein [KO:K16931]
1583  CYP11A1; cytochrome P450 family 11 subfamily A member 1 [KO:K00498] [EC:1.14.15.6]
1586  CYP17A1; cytochrome P450 family 17 subfamily A member 1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
3292  HSD17B1; hydroxysteroid 17-beta dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
3294  HSD17B2; hydroxysteroid 17-beta dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
8644  AKR1C3; aldo-keto reductase family 1 member C3 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
51478  HSD17B7; hydroxysteroid 17-beta dehydrogenase 7 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
3283  HSD3B1; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
3284  HSD3B2; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
2488  FSHB; follicle stimulating hormone subunit beta [KO:K05250]
2492  FSHR; follicle stimulating hormone receptor [KO:K04247]
1588  CYP19A1; cytochrome P450 family 19 subfamily A member 1 [KO:K07434] [EC:1.14.14.14]
1545  CYP1B1; cytochrome P450 family 1 subfamily B member 1 [KO:K07410] [EC:1.14.14.1]
1543  CYP1A1; cytochrome P450 family 1 subfamily A member 1 [KO:K07408] [EC:1.14.14.1]
9210  BMP15; bone morphogenetic protein 15 [KO:K05498]
654  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-Hydroxyestradiol-17beta
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
hsa00140  Steroid hormone biosynthesis
hsa04350  TGF-beta signaling pathway
hsa04910  Insulin signaling pathway
hsa04912  GnRH signaling pathway
KO pathway
ko04913   

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