KEGG PATHWAY: pteh04913

PATHWAY: pteh04913

Entry

pteh04913                   Pathway

Name

Ovarian steroidogenesis - Piliocolobus tephrosceles (Ugandan red Colobus)

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

pteh04913

Ovarian steroidogenesis

Other DBs

GO:

0050810

Organism

Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]

Gene

111538053

CGA; glycoprotein hormones alpha chain [KO:K08522]

111550407

LHCGR; lutropin-choriogonadotropic hormone receptor [KO:K04248]

111555637

GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X6 [KO:K04632]

111555638

neuroendocrine secretory protein 55 [KO:K04632]

111546755

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

111554419

ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]

111552878

ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]

111544335

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

111542054

ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]

111541238

ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]

111549769

ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]

111551667

ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]

111523821

PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]

111543418

PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]

111540404

PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]

111534477

cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]

113224231

cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]

111520161

PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]

111531132

PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]

111531141

PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]

111531158

PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]

111536920

PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]

111520549

acyl-coenzyme A thioesterase 1 isoform X1 [KO:K01068] [EC:3.1.2.2]

111520556

ACOT4; peroxisomal succinyl-coenzyme A thioesterase [KO:K01068] [EC:3.1.2.2]

111529801

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

111522986

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

111536921

PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]

111520623

INS; insulin isoform X1 [KO:K04526]

111522649

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

111523785

IGF1; insulin-like growth factor I isoform X1 [KO:K05459]

111548389

IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]

111527714

LDLR; low-density lipoprotein receptor [KO:K12473]

111552064

SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]

111544129

STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]

111529691

cholesterol side-chain cleavage enzyme, mitochondrial isoform X1 [KO:K00498] [EC:1.14.15.6]

111538851

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

111537362

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

111552544

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

111528985

aldo-keto reductase family 1 member C15-like isoform X1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

111528130

aldo-keto reductase family 1 member C3 homolog [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

113224919

LOW QUALITY PROTEIN: aldo-keto reductase family 1 member C15-like [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357]

111525046

HSD17B7; 3-keto-steroid reductase isoform X1 [KO:K13373] [EC:1.1.1.62 1.1.1.270]

111549591

3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]

111549589

3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1-like isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]

111554706

FSHB; follitropin subunit beta [KO:K05250]

111550444

FSHR; follicle-stimulating hormone receptor isoform X1 [KO:K04247]

111552757

aromatase [KO:K07434] [EC:1.14.14.14]

111545371

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

111529702

cytochrome P450 1A1 isoform X1 [KO:K07408] [EC:1.14.14.1]

111531421

BMP15; bone morphogenetic protein 15 [KO:K05498]

111548612

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