KEGG   PATHWAY: rn00140Help
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
Steroid hormone biosynthesis
rn00140

All organismsOrtholog table
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: 
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,reduced-flavoprotein:oxygen 19-oxidoreductase
R01841  
17alpha-Hydroxyprogesterone acetaldehyde-lyase
R01842  
Androstenedione 7alpha-hydroxylase
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,hydrogen-donor:oxygen oxidoreductase (17-alpha-hydroxylating)
R02213  
Progesterone,hydrogen-donor: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,reduced-flavoprotein: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,reduced-flavoprotein:oxygen 19-oxidoreductase
R02502  
17beta-hydroxysteroid UDP-glucuronosyltransferase
R02503  
testosterone 7alpha-hydroxylase
R02723  
 
R02725  
Androstenedione,reduced-adrenal-ferredoxin:oxygen oxidoreductase (11-hydroxylating)
R02834  
Cortisol:NAD+ 11-oxidoreductase
R02836  
Cortisol:NADP+ 11-oxidoreductase
R02838  
21-Deoxycortisol,hydrogen-donor: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,reduced-flavoprotein: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,hydrogen-donor: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,hydrogen-donor:oxygen oxidoreductase (17-alpha-hydroxylating)
R03784  
Pregnenolone,hydrogen-donor:oxygen oxidoreductase (21-hydroxylating)
R03847  
Corticosterone:NAD+ 11-oxidoreductase
R03848  
Corticosterone:NADP+ 11-oxidoreductase
R03849  
11beta-Hydroxyprogesterone,hydrogen-donor: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,hydrogen-donor: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,reduced-flavoprotein:oxygen 19-oxidoreductase
R04760  
 
R04761  
19-hydroxytestosterone,reduced-flavoprotein: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  
Steroid,hydrogen-donor:oxygen oxidoreductase (17-alpha-hydroxylating)
R04853  
20alpha-Hydroxycholesterol,hydrogen-donor:oxygen oxidoreductase (17-alpha-hydroxylating)
R04854  
20alpha-Hydroxycholesterol:oxygen oxidoreductase (side-chain-cleaving)
R04855  
22beta-Hydroxycholesterol:oxygen oxidoreductase (side-chain-cleaving)
R08516  
17alpha-Hydroxypregnenolone acetaldehyde-lyase
R08517  
17alpha-hydroxypregnenolone,hydrogen-donor:oxygen oxidoreductase (side-chain-cleaving, acetate-formig)
R08518  
17alpha-hydroxyprogesterone,hydrogen-donor:oxygen oxidoreductase (side-chain-cleaving, acetate-formig)
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  
3beta-hydroxyandrost-5-en-17-one,NADPH: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  
3alpha-Hydroxy-5beta-pregnane-20-one
C05481  
Cortolone
C05482  
Cortol
C05483  
3alpha,20alpha,21-Trihydroxy-5beta-pregnane-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  
3alpha-Hydroxy-5alpha-pregnan-20-one
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)
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)
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)
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)
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)
Reference
  Authors
Holmes MC, Seckl JR
  Title
The role of 11beta-hydroxysteroid dehydrogenases in the brain.
  Journal
Mol Cell Endocrinol 248:9-14 (2006)
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)
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)
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)
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)
KO pathway
 

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