KEGG PATHWAY: tup04913

PATHWAY: tup04913

Entry

tup04913                    Pathway

Name

Ovarian steroidogenesis - Tupaia chinensis (Chinese tree shrew)

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

tup04913

Ovarian steroidogenesis

Other DBs

GO:

0050810

Organism

Tupaia chinensis (Chinese tree shrew) [GN:tup]

Gene

102467691

CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]

102486798

LHCGR; luteinizing hormone/choriogonadotropin receptor [KO:K04248]

102489563

GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]

102501321

neuroendocrine secretory protein 55 [KO:K04632]

102468873

ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]

102492353

ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]

102477532

ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]

102490273

ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]

102490639

ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]

102468478

ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]

102496578

ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]

102472317

ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]

102477344

ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]

102502506

PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]

102478525

PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]

102473333

PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]

102470223

PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]

102471767

PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]

102472618

JMJD7; jmjC domain-containing protein 7 [KO:K16342] [EC:3.1.1.4]

102470647

PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]

102477396

PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]

102502559

ACOT4; acyl-CoA thioesterase 4 [KO:K01068] [EC:3.1.2.2]

102502991

ACOT2; acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]

102487858

acyl-coenzyme A thioesterase 1 [KO:K01068] [EC:3.1.2.2]

102480526

ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]

102491196

cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

102492447

cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

102491623

cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

102492033

cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

102490783

cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

102478264

PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]

102481191

INS; insulin [KO:K04526]

102469167

INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]

102490248

IGF1; insulin like growth factor 1 [KO:K05459]

102473496

IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]

102484417

LDLR; low density lipoprotein receptor [KO:K12473]

102502354

SCARB1; scavenger receptor class B member 1 [KO:K13885]

102488286

STAR; steroidogenic acute regulatory protein [KO:K16931]

102487565

cholesterol side-chain cleavage enzyme, mitochondrial-like [KO:K00498] [EC:1.14.15.6]

102472543

steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]

102482283

HSD17B1; hydroxysteroid 17-beta dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]

102481564

HSD17B2; hydroxysteroid 17-beta dehydrogenase 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239]

102491222

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]

102491650

prostaglandin-E(2) 9-reductase-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

102478495

prostaglandin-E(2) 9-reductase [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

102478063

aldo-keto reductase family 1 member C4 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

102473205

HSD17B7; hydroxysteroid 17-beta dehydrogenase 7 [KO:K13373] [EC:1.1.1.62 1.1.1.270]

102470981

3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase-like [KO:K00070] [EC:1.1.1.145 5.3.3.1]

102494116

gonadotropin subunit beta-1-like [KO:K05250]

102490240

FSHB; follitropin subunit beta [KO:K05250]

102487198

FSHR; follicle stimulating hormone receptor [KO:K04247]

102503106

aromatase [KO:K07434] [EC:1.14.14.14]

102492978

cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]

102484009

cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]

102501630

BMP15; bone morphogenetic protein 15 [KO:K05498]

102471047

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

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