KEGG   PATHWAY: rno04913
Entry
rno04913                    Pathway                                
Name
Ovarian steroidogenesis - Rattus norvegicus (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
rno04913  Ovarian steroidogenesis
rno04913

Other DBs
GO: 0050810
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
116700  Cga; glycoprotein hormones alpha chain precursor [KO:K08522]
25329  Lhb; lutropin subunit beta isoform 1 precursor [KO:K08521]
25477  Lhcgr; lutropin-choriogonadotropic hormone receptor precursor [KO:K04248]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
50559  Acot1; acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]
192272  Acot2; acyl-coenzyme A thioesterase 2, mitochondrial [KO:K01068] [EC:3.1.2.2]
314304  Acot3; acyl-CoA thioesterase 3 [KO:K01068] [EC:3.1.2.2]
503049  Acot5; acyl-coenzyme A thioesterase 5 [KO:K01068] [EC:3.1.2.2]
681337  Acot4; acyl-coenzyme A thioesterase 4 [KO:K01068] [EC:3.1.2.2]
25290  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
502969  Cyp2j16; cytochrome P450 2J4-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
313375  Cyp2j3; cytochrome P450 2J3 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
313373  Cyp2j10; cytochrome P450, family 2, subfamily j, polypeptide 10 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100912642  cytochrome P450 2J4-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
65210  Cyp2j4; cytochrome P450 2J4 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
24506  Ins2; insulin-2 preproprotein [KO:K04526]
24505  Ins1; insulin-1 preproprotein [KO:K04526]
24954  Insr; insulin receptor preproprotein [KO:K04527] [EC:2.7.10.1]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
25718  Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087] [EC:2.7.10.1]
300438  Ldlr; low-density lipoprotein receptor precursor [KO:K12473]
25073  Scarb1; scavenger receptor class B member 1 [KO:K13885]
25557  Star; steroidogenic acute regulatory protein, mitochondrial precursor [KO:K16931]
29680  Cyp11a1; cholesterol side-chain cleavage enzyme, mitochondrial precursor [KO:K00498] [EC:1.14.15.6]
25146  Cyp17a1; steroid 17-alpha-hydroxylase/17,20 lyase precursor [KO:K00512] [EC:1.14.14.19 1.14.14.32]
25322  Hsd17b1; estradiol 17-beta-dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
79243  Hsd17b2; estradiol 17-beta-dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]
361267  Akr1c15; aldo-keto reductase family 1 member C15 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]
29540  Hsd17b7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 [KO:K13373] [EC:1.1.1.62 1.1.1.270]
29632  Hsd3b2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 4 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
360348  Hsd3b1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
24470  Hsd3b5; NADPH-dependent 3-keto-steroid reductase Hsd3b5 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
682974  Hsd3b3; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
25447  Fshb; follitropin subunit beta precursor [KO:K05250]
25449  Fshr; follicle-stimulating hormone receptor precursor [KO:K04247]
25147  Cyp19a1; aromatase [KO:K07434] [EC:1.14.14.14]
25426  Cyp1b1; cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
24296  Cyp1a1; cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
59302  Bmp15; bone morphogenetic protein 15 precursor [KO:K05498]
25644  Bmp6; bone morphogenetic protein 6 precursor [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
rno00140  Steroid hormone biosynthesis
rno04350  TGF-beta signaling pathway
rno04910  Insulin signaling pathway
rno04912  GnRH signaling pathway
KO pathway
ko04913   

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Genome (1)   
   KEGG GENOME (1)   
Gene (58)   
   KEGG GENES (58)   
All databases (59)   

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