KEGG   PATHWAY: rn00140
Entry
rn00140                     Pathway                                

Name
Steroid hormone biosynthesis
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
Pathway map
rn00140  Steroid hormone biosynthesis
rn00140

Module
M00107  Steroid hormone biosynthesis, cholesterol => prognenolone => progesterone [PATH:rn00140]
M00108  C21-Steroid hormone biosynthesis, progesterone => corticosterone/aldosterone [PATH:rn00140]
M00109  C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone [PATH:rn00140]
M00110  C19/C18-Steroid hormone biosynthesis, pregnenolone => androstenedione => estrone [PATH:rn00140]
Other DBs
GO: 0034754
Reaction
R00535  3'-Phosphoadenylylsulfate:17beta-estradiol 3-sulfotransferase
R00536  3'-Phosphoadenylylsulfate:phenolic-steroid sulfotransferase
R00537  3'-Phosphoadenylylsulfate:phenolic-steroid sulfotransferase
R01454  Cholesterol:oxygen oxidoreductase (side-chain-cleaving)
R01833  Androst-4-ene-3,17-dione,hydrogen-donor:oxygen oxidoreductase (13-hydroxylating, lactonizing)
R01835  5beta-androstane-3,17-dione:NADP+ 4,5-oxidoreductase
R01836  testosterone:NAD+ 17-oxidoreductase
R01837  3beta-Hydroxyandrost-5-en-17-one:NAD+ 3-oxidoreductase/delta5-delta-4 isomerase
R01838  testosterone:NADP+ 17-oxidoreductase
R01840  androstenedione,NADPH---hemoprotein reductase:oxygen oxidoreductase (19-hydroxylating)
R01842  androstenedione,NADPH---hemoprotein reductase:oxygen oxidoreductase (7alpha-hydroxylating)
R02207  20alpha-Hydroxy-4-pregnen-3-one:NAD+ 20-oxidoreductase
R02208  5alpha-pregnane-3,20-dione:NADP+ delta4-oxidoreductase
R02209  20alpha-Hydroxy-4-pregnen-3-one:NADP+ 20-oxidoreductase
R02211  progesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R02213  progesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R02214  Progesterone,hydrogen-donor:oxygen oxidoreductase (11alpha-hydroxylating)
R02215  5beta-Pregnane-3,20-dione:(acceptor) delta4-oxidoreductase
R02216  Pregnenolone:NAD+ 3-oxidoreductase
R02218  progesterone,reduced ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R02219  3-Oxo-5beta-steroid:NADP+ delta4-oxidoreductase
R02347  Estradiol-17alpha:NAD+ 17-oxidoreductase
R02349  Estradiol-17alpha:NADP+ 16-oxidoreductase
R02350  3'-Phosphoadenylylsulfate:estrone 3-sulfotransferase
R02351  19-oxoandrostenedione,NADPH---hemoprotein reductase:oxygen oxidoreductase (aromatizing, formate-forming)
R02352  Estradiol-17beta:NAD+ 17-oxidoreductase
R02353  Estradiol-17beta:NADP+ 17-oxidoreductase
R02354   
R02355   
R02356   
R02358  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R02476  Androsterone:NAD+ oxidoreductase
R02477  Androsterone:NADP+ oxidoreductase
R02478  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R02497  dihydrotestosterone:NADP+ delta4-oxidoreductase
R02498  5beta-dihydrotestosterone:NADP+ 4,5-oxidoreductase
R02499  Testosterone delta5-delat4-isomerase
R02501  testosterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (19-hydroxylating)
R02502  17beta-hydroxysteroid UDP-glucuronosyltransferase
R02503  testosterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (7alpha-hydroxylating)
R02723   
R02725  Androstenedione,reduced-adrenal-ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R02834  Cortisol:NAD+ 11-oxidoreductase
R02836  Cortisol:NADP+ 11-oxidoreductase
R02838  21-deoxycortisol,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R02840  Cortisol delta5-delat4-isomerase
R02841  11beta,17alpha,21-Trihydroxy-5beta-pregnane-3,20-dione:NADP+ delta4-oxidoreductase
R02843  steroid,reduced ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R02893  17alpha,21-dihydroxy-5beta-pregnane-3,11,20-trione:NADP+ delta4-oxidoreductase
R03086  Estradiol-17beta,hydrogen-donor:oxygen oxidoreductase (6beta-hydroxylating)
R03087  19-oxotestosterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (aromatizing, formate-forming)
R03088   
R03089   
R03090   
R03091  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R03262  Corticosterone,reduced-adrenal-ferredoxin:oxygen oxidoreductase (18-hydroxylating)
R03263   
R03325  17alpha,20alpha-Dihydroxypregn-4-en-3-one:NADP+ 20-oxidoreductase
R03326  17alpha-hydroxyprogesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R03327  17alpha-Hydroxypregnenolone:NAD+ 3-oxidoreductase
R03329  steroid,reduced-adrenal-ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R03404  3beta-Hydroxyandrost-5-en-17-one 3-sulfate sulfohydrolase
R03405  3'-phosphoadenylylsulfate:alcohol sulfotransferase
R03406  Androst-5-ene-3beta,17beta-diol:NAD+ oxidoreductase
R03407  Androst-5-ene-3beta,17beta-diol:NADP+ oxidoreductase
R03408   
R03713  11beta,21-Dihydroxy-3,20-oxo-5beta-pregnan-18-al:NADP+ delta4-oxidoreductase
R03783  pregnenolone,NADPH-hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R03784  pregnenolone,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R03847  Corticosterone:NAD+ 11-oxidoreductase
R03848  Corticosterone:NADP+ 11-oxidoreductase
R03849  11beta-hydroxyprogesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R03851  11-deoxycorticosterone,reduced ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R03933  20alpha,22beta-Dihydroxycholesterol,ferredoxin:oxygen oxidoreductase (side-chain-cleaving)
R03980  Estrone 3-sulfate sulfohydrolase
R04163  21-Hydroxypregnenolone:NAD+ 3-oxidoreductase
R04309  3alpha-Hydroxy-5beta-androstan-17-one:NAD+ oxidoreductase (B-specific)
R04310  3alpha-Hydroxy-5beta-androstan-17-one:NADP+ oxidoreductase (B-specific)
R04352  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R04353  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R04354  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R04675  17alpha-hydroxypregnenolone,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
R04676  17alpha,20alpha-Dihydroxycholesterol:oxygen oxidoreductase (side-chain-cleaving)
R04678  16alpha-Hydroxyandrost-4-ene-3,17-dione delta5-delat4-isomerase
R04681  Estriol:NAD+ 17-oxidoreductase
R04682  Estriol:NADP+ 17-oxidoreductase
R04683  UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R04758  11beta-Hydroxyandrost-4-ene-3,17-dione:NADP+ 11-oxidoreductase
R04759  19-hydroxyandrostenedione,NADPH---hemoprotein reductase:oxygen 19-oxidoreductase
R04760   
R04761  19-hydroxytestosterone,NADPH---hemoprotein reductase:oxygen 19-oxidoreductase
R04762  S-adenosyl-L-methionine:2-Hydroxyestrone O-methyltransferase
R04764   
R04829  Urocortisone:NAD+ oxidoreductase (B-specific)
R04830  Urocortisone:NADP+ oxidoreductase (B-specific)
R04831  Cortolone:NAD+ oxidoreductase
R04832  Urocortisol:NAD+ oxidoreductase (B-specific)
R04833  Urocortisol:NADP+ oxidoreductase (B-specific)
R04834  Cortol:NAD+ oxidoreductase
R04835  3alpha,11beta,21-Trihydroxy-20-oxo-5beta-pregnan-18-al:NAD+ oxidoreductase (B-specific)
R04836  3alpha,11beta,21-Trihydroxy-20-oxo-5beta-pregnan-18-al:NADP+ oxidoreductase (B-specific)
R04837  Tetrahydrocorticosterone:NAD+ oxidoreductase (B-specific)
R04838  Tetrahydrocorticosterone:NADP+ oxidoreductase (B-specific)
R04840  Tetrahydrocorticosterone:NADP+ 11-oxidoreductase
R04842  3alpha,21-Dihydroxy-5beta-pregnane-11,20-dione:NAD+ oxidoreductase (B-specific)
R04843  3alpha,21-Dihydroxy-5beta-pregnane-11,20-dione:NADP+ oxidoreductase (B-specific)
R04844  3alpha,20alpha,21-Trihydroxy-5beta-pregnane-11-one:NAD+ oxidoreductase
R04845  3alpha-Hydroxy-5beta-pregnane-20-one:NAD+ oxidoreductase (B-specific)
R04846  3alpha-Hydroxy-5beta-pregnane-20-one:NADP+ oxidoreductase (B-specific)
R04847  Pregnanediol:NAD+ oxidoreductase
R04849  11-Deoxycortisol delta5-delat4-isomerase
R04850  17alpha,21-dihydroxypregnenolone:oxygen oxidoreductase (11-hydroxylating)
R04852  11beta-hydroxyprogesterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R04853  20alpha-hydroxycholesterol,NADPH-hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R04854  20alpha-Hydroxycholesterol:oxygen oxidoreductase (side-chain-cleaving)
R04855  22beta-Hydroxycholesterol:oxygen oxidoreductase (side-chain-cleaving)
R08517  17alpha-Hydroxypregnenolone,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)
R08518  17alpha-hydroxyprogesterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)
R08941  Cholesterol-sulfate sulfohydrolase
R08942  Pregnenolone-sulfate sulfohydrolase
R08943  pregnenolone,NADPH:oxygen oxidoreductase (7alpha-hydroxylating)
R08945  11beta,17beta-dihydroxy-4-androsten-3-one:NAD+ 17-oxidoreductase
R08953   
R08954  5alpha-dihydrodeoxycorticosterone:NADP+ delta4-oxidoreductase
R08955  3alpha,21-dihydroxy-5alpha-pregnan-20-one:NADP+ 3-oxidoreductase (A-specific)
R08957  3alpha-hydroxy-5alpha-pregnan-20-one:NADP+ 3-oxidoreductase (A-specific)
R08958  5alpha-pregnan-20alpha-ol-3-one:NADP+ 20-oxidoreductase
R08959  5alpha-pregnane-3alpha,20alpha-diol:NADP+ 20-oxidoreductase
R08960  5alpha-pregnane-3alpha,20alpha-diol:NADP+ oxidoreductase (A-specific)
R08961  dehydroepiandrosterone,NADPH-hemoprotein reductase:oxygen oxidoreductase (7alpha-hydroxylating)
R08963  Androstan-3alpha,17beta-diol:NADP+ oxidoreductase
R08977  3'-phosphoadenylyl-sulfate:cholesterol sulfotransferase
R08978  3'-phosphoadenylyl-sulfate:pregnenolone sulfotransferase
R08980  11beta,17beta-dihydroxy-4-androsten-3-one:NADP+ 17-oxidoreductase
R08994   
R08995   
R10242  5alpha-androstane-3,17-dione:NADP+ delta4-oxidoreductase
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
Related
pathway
rn00100  Steroid biosynthesis
KO pathway
ko00140   

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