KEGG   PATHWAY: ecb00140Help
Entry
ecb00140                    Pathway                                

Name
Steroid hormone biosynthesis - Equus caballus (horse)
Description
Steroid hormones derived from cholesterol are a class of biologically active compounds in vertebrates. The cholesterol side-chain cleavage enzyme CYP11A1 catalyzes conversion of cholesterol, a C27 compound, to the first C21 steroid, pregnenolone, which is converted by a bifunctional enzyme complex to the gestagen hormone, progesterone [MD:M00107]. Pregnenolone and progesterone are the starting materials for the three groups of steroids: C21 steroids of glucocorticoids and mineralocorticoids, C19 steroids of androgens, and C18 steroids of estrogens. (i) Progesterone is converted by hydroxylations at carbons 21 and 11 to corticosterone, which is further modified by hydroxylation and oxydoreduction at carbon 18 to yield aldosterone, a mineralcorticoid [MD:M00108]. Cortisol, the main glucocorticoid, is formed from 17alpha-hydroxyprogesterone with 11-deoxycortisol as an intermediate [MD:M00109]. (ii) Male hormone testosterone is formed from pregnenolone by two pathways, delta5 pathway via dehydroepiandrosterone and delta4 pathway via androstenedione [MD:M00110]. The enzyme CYP17A1 is responsible for the 17,20 lyase and 17alpha-hydroxylase activities in respective pathways. (iii) Female hormones estrone and estradiol are formed from testosterone and 4-androstene-3,17-dione by oxidative removal of the C19 methyl group and subsequent aromatization of ring A [MD:M00111]. In addition to these three groups, recent studies show that there is another group, termed neurosteroids, synthesized in the brain rather than the peripheral endocrine gland.
Class
Metabolism; Lipid metabolism
BRITE hierarchy
Pathway map
ecb00140  Steroid hormone biosynthesis
ecb00140

Ortholog table
Module
ecb_M00107  Steroid hormone biosynthesis, cholesterol => prognenolone => progesterone [PATH:ecb00140]
ecb_M00109  C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone [PATH:ecb00140]
ecb_M00110  C19/C18-Steroid hormone biosynthesis, pregnenolone => androstenedione => estrone [PATH:ecb00140]
Other DBs
BSID: 94721
GO: 0034754
Organism
Equus caballus (horse) [GN:ecb]
Gene
100034229  CYP11A1; cholesterol side-chain cleavage enzyme, mitochondrial precursor [KO:K00498] [EC:1.14.15.6]
100034232  CYP17A1; steroid 17-alpha-hydroxylase/17,20 lyase precursor [KO:K00512] [EC:1.14.14.32 1.14.14.19]
100034102  STS; steryl-sulfatase precursor [KO:K01131] [EC:3.1.6.2]
100147584  SULT2B1; sulfotransferase family cytosolic 2B member 1 [KO:K01015] [EC:2.8.2.2]
100059277  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
100034078  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase [KO:K00070] [EC:5.3.3.1 1.1.1.145]
100071450  SRD5A1; 3-oxo-5-alpha-steroid 4-dehydrogenase 1 isoform X1 [KO:K12343] [EC:1.3.1.22]
100070655  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
100059582  SRD5A3; polyprenol reductase [KO:K12345] [EC:1.3.1.94 1.3.1.22]
100070616  aldo-keto reductase family 1 member C23-like protein [KO:K04119] [EC:1.1.1.357 1.1.1.213 1.1.1.188 1.1.1.51]
100063645  cytochrome P450 11B1, mitochondrial [KO:K00497] [EC:1.14.15.4]
100063612  cytochrome P450 11B1, mitochondrial-like [KO:K00497] [EC:1.14.15.4]
100066919  AKR1D1; 3-oxo-5-beta-steroid 4-dehydrogenase [KO:K00251] [EC:1.3.1.3]
100056429  HSD11B1; corticosteroid 11-beta-dehydrogenase isozyme 1 [KO:K15680] [EC:1.1.1.146]
100034124  HSD11B2; corticosteroid 11-beta-dehydrogenase isozyme 2 [KO:K00071] [EC:1.1.1.-]
100070570  aldo-keto reductase family 1 member C23 [KO:K00212] [EC:1.3.1.20 1.1.1.357 1.1.1.149]
100064741  25-hydroxycholesterol 7-alpha-hydroxylase [KO:K07430] [EC:1.14.14.29]
100034106  SULT1E1; estrogen sulfotransferase [KO:K01016] [EC:2.8.2.4]
102148009  estrogen sulfotransferase [KO:K01016] [EC:2.8.2.4]
100036556  HSD17B1; estradiol 17-beta-dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
100146214  HSD17B2; estradiol 17-beta-dehydrogenase 2 isoform X2 [KO:K13368] [EC:1.1.1.239 1.1.1.62]
100052840  17-beta-hydroxysteroid dehydrogenase type 6 isoform X2 [KO:K13369] [EC:1.1.1.239 1.1.1.105 1.1.1.62]
100052892  uncharacterized LOC100052892 [KO:K13369] [EC:1.1.1.239 1.1.1.105 1.1.1.62]
100059061  HSD17B7; 3-keto-steroid reductase isoform X3 [KO:K13373] [EC:1.1.1.270 1.1.1.62]
100061414  HSD17B8; estradiol 17-beta-dehydrogenase 8 isoform X3 [KO:K13370] [EC:1.1.1.239 1.1.1.62]
100050075  HSD17B12; very-long-chain 3-oxoacyl-CoA reductase [KO:K10251] [EC:1.1.1.330 1.1.1.62]
100070719  very-long-chain 3-oxoacyl-CoA reductase-B-like isoform X1 [KO:K10251] [EC:1.1.1.330 1.1.1.62]
100062285  CYP1A1; cytochrome P450 1A1 [KO:K07408] [EC:1.14.14.1]
100062244  CYP1A2; cytochrome P450 1A2 isoform X2 [KO:K07409] [EC:1.14.14.1]
100068569  cytochrome P450 2B4 [KO:K07412] [EC:1.14.14.1]
100068603  cytochrome P450 2B11-like precursor [KO:K07412] [EC:1.14.14.1]
100061579  CYP2C113; cytochrome P450 2C19-like precursor [KO:K07413] [EC:1.14.14.1]
100061367  cytochrome P450 2C21 [KO:K07413] [EC:1.14.14.1]
100061400  cytochrome P450 2C21 [KO:K07413] [EC:1.14.14.1]
100070400  cytochrome P450 2C23 [KO:K07413] [EC:1.14.14.1]
100070895  cytochrome P450 2D14 isoform X2 [KO:K07414] [EC:1.14.14.1]
100056087  cytochrome P450 2D14 [KO:K07414] [EC:1.14.14.1]
100070962  cytochrome P450 2D14 isoform X2 [KO:K07414] [EC:1.14.14.1]
100146596  cytochrome P450 2D14 isoform X1 [KO:K07414] [EC:1.14.14.1]
100070990  cytochrome P450 2D14-like [KO:K07414] [EC:1.14.14.1]
100070905  cytochrome P450 2D14 isoform X1 [KO:K07414] [EC:1.14.14.1]
100070945  CYP2D50; cytochrome P450 2D50 [KO:K07414] [EC:1.14.14.1]
100147428  cytochrome P450 2D14-like [KO:K07414] [EC:1.14.14.1]
100147480  cytochrome P450 2D14 isoform X1 [KO:K07414] [EC:1.14.14.1]
100067064  CYP3A89; cytochrome P450 3A89 [KO:K07424] [EC:1.14.14.1]
100067084  CYP3A94; cytochrome p450 3A94 [KO:K07424] [EC:1.14.14.1]
100067041  CYP3A93; cytochrome p450 3A93 [KO:K07424] [EC:1.14.14.1]
100067109  CYP3A95; cytochrome p450 3A95 [KO:K07424] [EC:1.14.14.1]
100067131  CYP3A96; cytochrome P450 3A96 [KO:K07424] [EC:1.14.14.1]
100066422  CYP2E1; cytochrome P450 2E1 [KO:K07415] [EC:1.14.13.-]
100070088  CYP1B1; cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1]
100009712  CYP19A1; aromatase [KO:K07434] [EC:1.14.14.14]
100052888  cholesterol 7-alpha-monooxygenase [KO:K00489] [EC:1.14.14.23]
100068176  UGT2A2; UDP-glucuronosyltransferase 2A2 isoform X2 [KO:K00699] [EC:2.4.1.17]
100066444  UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100065342  UDP-glucuronosyltransferase 1-1 isoform X1 [KO:K00699] [EC:2.4.1.17]
100066472  UDP-glucuronosyltransferase 2B31 isoform X1 [KO:K00699] [EC:2.4.1.17]
100146977  UDP-glucuronosyltransferase 2C1 [KO:K00699] [EC:2.4.1.17]
100066329  UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100066359  UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100066501  UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100067994  UDP-glucuronosyltransferase 2C1 isoform X1 [KO:K00699] [EC:2.4.1.17]
100068026  UDP-glucuronosyltransferase 2C1 isoform X1 [KO:K00699] [EC:2.4.1.17]
100068041  UDP-glucuronosyltransferase 2C1-like [KO:K00699] [EC:2.4.1.17]
100146509  COMT; catechol O-methyltransferase isoform MB-COMT [KO:K00545] [EC:2.1.1.6]
100062795  HSD17B3; testosterone 17-beta-dehydrogenase 3 isoform X1 [KO:K10207] [EC:1.1.1.64]
Compound
C00187  Cholesterol
C00280  Androstenedione
C00410  Progesterone
C00468  Estrone
C00523  Androsterone
C00535  Testosterone
C00674  5alpha-Androstane-3,17-dione
C00735  Cortisol
C00762  Cortisone
C00951  Estradiol-17beta
C01124  18-Hydroxycorticosterone
C01176  17alpha-Hydroxyprogesterone
C01227  Dehydroepiandrosterone
C01780  Aldosterone
C01953  Pregnenolone
C02140  Corticosterone
C02373  4-Methylpentanal
C02537  Estradiol-17alpha
C02538  Estrone 3-sulfate
C03205  11-Deoxycorticosterone
C03681  5alpha-Pregnane-3,20-dione
C03747  11alpha-Hydroxyprogesterone
C03772  5beta-Androstane-3,17-dione
C03852  Androstan-3alpha,17beta-diol
C03917  Dihydrotestosterone
C03935  6beta-Hydroxy-17beta-estradiol
C04042  20alpha-Hydroxy-4-pregnen-3-one
C04295  Androstenediol
C04373  Etiocholanolone
C04518  17alpha,20alpha-Dihydroxypregn-4-en-3-one
C04555  Dehydroepiandrosterone sulfate
C04676  Testololactone
C05138  17alpha-Hydroxypregnenolone
C05139  16alpha-Hydroxydehydroepiandrosterone
C05140  16alpha-Hydroxyandrost-4-ene-3,17-dione
C05141  Estriol
C05284  11beta-Hydroxyandrost-4-ene-3,17-dione
C05285  Adrenosterone
C05290  19-Hydroxyandrost-4-ene-3,17-dione
C05291  7alpha-Hydroxytestosterone
C05293  5beta-Dihydrotestosterone
C05294  19-Hydroxytestosterone
C05295  19-Oxotestosterone
C05296  7alpha-Hydroxyandrost-4-ene-3,17-dione
C05297  19-Oxoandrost-4-ene-3,17-dione
C05298  2-Hydroxyestrone
C05299  2-Methoxyestrone
C05300  16alpha-Hydroxyestrone
C05301  2-Hydroxyestradiol
C05302  2-Methoxy-17beta-estradiol
C05469  17alpha,21-Dihydroxy-5beta-pregnane-3,11,20-trione
C05470  Tetrahydrocortisone
C05471  11beta,17alpha,21-Trihydroxy-5beta-pregnane-3,20-dione
C05472  Urocortisol
C05473  11beta,21-Dihydroxy-3,20-oxo-5beta-pregnan-18-al
C05474  3alpha,11beta,21-Trihydroxy-20-oxo-5beta-pregnan-18-al
C05475  11beta,21-Dihydroxy-5beta-pregnane-3,20-dione
C05476  Tetrahydrocorticosterone
C05477  21-Hydroxy-5beta-pregnane-3,11,20-trione
C05478  3alpha,21-Dihydroxy-5beta-pregnane-11,20-dione
C05479  5beta-Pregnane-3,20-dione
C05480  Pregnanolone
C05481  Cortolone
C05482  Cortol
C05483  3alpha,20alpha,21-Trihydroxy-5beta-pregnan-11-one
C05484  Pregnanediol
C05485  21-Hydroxypregnenolone
C05487  17alpha,21-Dihydroxypregnenolone
C05488  11-Deoxycortisol
C05489  11beta,17alpha,21-Trihydroxypregnenolone
C05490  11-Dehydrocorticosterone
C05497  21-Deoxycortisol
C05498  11beta-Hydroxyprogesterone
C05499  17alpha,20alpha-Dihydroxycholesterol
C05500  20alpha-Hydroxycholesterol
C05501  20alpha,22beta-Dihydroxycholesterol
C05502  22(R)-Hydroxycholesterol
C05503  Estradiol-17beta 3-glucuronide
C05504  16-Glucuronide-estriol
C08357  Estradiol-17beta 3-sulfate
C08358  2-Methoxyestrone 3-sulfate
C08359  2-Methoxyestradiol-17beta 3-sulfate
C11131  2-Methoxy-estradiol-17beta 3-glucuronide
C11132  2-Methoxyestrone 3-glucuronide
C11133  Estrone glucuronide
C11134  Testosterone glucuronide
C11135  Androsterone glucuronide
C11136  Etiocholan-3alpha-ol-17-one 3-glucuronide
C13712  Allopregnanolone
C13713  Allotetrahydrodeoxycorticosterone
C18038  7alpha-Hydroxypregnenolone
C18039  Aldosterone hemiacetal
C18040  5alpha-Dihydrodeoxycorticosterone
C18041  5alpha-Pregnan-20alpha-ol-3-one
C18042  5alpha-Pregnane-3alpha,20alpha-diol
C18043  Cholesterol sulfate
C18044  3beta-Hydroxypregn-5-en-20-one sulfate
C18045  7alpha-Hydroxydehydroepiandrosterone
C18075  11beta,17beta-Dihydroxy-4-androsten-3-one
Reference
  Authors
Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K
  Title
Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones.
  Journal
Biochem J 351:67-77 (2000)
DOI:10.1042/bj3510067
Reference
  Authors
Tomlinson JW, Stewart PM
  Title
Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase.
  Journal
Best Pract Res Clin Endocrinol Metab 15:61-78 (2001)
DOI:10.1053/beem.2000.0119
Reference
  Authors
Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A
  Title
Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.
  Journal
Chem Biol Interact 143-144:503-13 (2003)
DOI:10.1016/S0009-2797(02)00206-5
Reference
  Authors
Thomas JL, Duax WL, Addlagatta A, Brandt S, Fuller RR, Norris W
  Title
Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1 3 beta-hydroxysteroid dehydrogenase/isomerase.
  Journal
J Biol Chem 278:35483-90 (2003)
DOI:10.1074/jbc.M304752200
Reference
  Authors
Cavigelli SA, Monfort SL, Whitney TK, Mechref YS, Novotny M, McClintock MK
  Title
Frequent serial fecal corticoid measures from rats reflect circadian and ovarian corticosterone rhythms.
  Journal
J Endocrinol 184:153-63 (2005)
DOI:10.1677/joe.1.05935
Reference
  Authors
Holmes MC, Seckl JR
  Title
The role of 11beta-hydroxysteroid dehydrogenases in the brain.
  Journal
Mol Cell Endocrinol 248:9-14 (2006)
DOI:10.1016/j.mce.2005.12.002
Reference
  Authors
Matsunaga T, Shintani S, Hara A
  Title
Multiplicity of mammalian reductases for xenobiotic carbonyl compounds.
  Journal
Drug Metab Pharmacokinet 21:1-18 (2006)
DOI:10.2133/dmpk.21.1
Reference
  Authors
Morris DJ, Latif SA, Hardy MP, Brem AS
  Title
Endogenous inhibitors (GALFs) of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2: derivatives of adrenally produced corticosterone and cortisol.
  Journal
J Steroid Biochem Mol Biol 104:161-8 (2007)
DOI:10.1016/j.jsbmb.2007.03.020
Reference
  Authors
Sanai M, Endo S, Matsunaga T, Ishikura S, Tajima K, El-Kabbani O, Hara A
  Title
Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.
  Journal
Arch Biochem Biophys 464:122-9 (2007)
DOI:10.1016/j.abb.2007.04.003
Reference
  Authors
Ghayee HK, Auchus RJ
  Title
Basic concepts and recent developments in human steroid hormone biosynthesis.
  Journal
Rev Endocr Metab Disord 8:289-300 (2007)
DOI:10.1007/s11154-007-9052-2
KO pathway
ko00140   
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