PATHWAY: rn00140 Help
Entry
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. 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
Ortholog table
Module
M00107 Steroid hormone biosynthesis, cholesterol => pregnenolone => 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 ]
M00976 C19-Steroid hormone biosynthesis, pregnenolone => testosterone => dihydrotestosterone [PATH:rn00140 ]
M00977 C19-Steroid hormone biosynthesis (androgen backdoor pathway), pregnenolone => androsterone => dihydrotestosterone [PATH:rn00140 ]
Other DBs
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
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)
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)
R03091 UDPglucuronate beta-D-glucuronosyltransferase(acceptor-unspecific)
R03262 corticosterone,reduced-adrenal-ferredoxin:oxygen oxidoreductase (18-hydroxylating)
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
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)
R04330 androstan-3alpha,17beta-diol:NAD+ oxidoreductase
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
R04761 19-hydroxytestosterone,NADPH---hemoprotein reductase:oxygen 19-oxidoreductase
R04762 S-adenosyl-L-methionine:2-hydroxyestrone O-methyltransferase
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
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
R10242 5alpha-androstane-3,17-dione:NADP+ delta4-oxidoreductase
R13212 5alpha-pregnane-3,20-dione,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R13213 allopregnanolone,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating)
R13215 5alpha-pregnan-17alpha-ol-3,20-dione:NADP+ Delta4-oxidoreductase
R13216 5alpha-pregnane-3alpha,17alpha-diol-20-one:NAD+ oxidoreductase
R13217 5alpha-pregnane-3alpha,17alpha-diol-20-one:NADP+ 3-oxidoreductase
R13218 5alpha-pregnane-3alpha,17alpha-diol-20-one,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)
R13219 androstan-3alpha,17beta-diol:NADP+ 17-oxidoreductase
R13220 dihydrotestosterone:NADP+ 17-oxidoreductase
R13221 dihydrotestosterone:NAD+ 17-oxidoreductase
Compound
C00674 5alpha-Androstane-3,17-dione
C01124 18-Hydroxycorticosterone
C01176 17alpha-Hydroxyprogesterone
C03681 5alpha-Pregnane-3,20-dione
C03747 11alpha-Hydroxyprogesterone
C03772 5beta-Androstane-3,17-dione
C03852 Androstan-3alpha,17beta-diol
C03935 6beta-Hydroxy-17beta-estradiol
C04042 20alpha-Hydroxy-4-pregnen-3-one
C04518 17alpha,20alpha-Dihydroxypregn-4-en-3-one
C04555 Dehydroepiandrosterone sulfate
C05138 17alpha-Hydroxypregnenolone
C05139 16alpha-Hydroxydehydroepiandrosterone
C05140 16alpha-Hydroxyandrost-4-ene-3,17-dione
C05284 11beta-Hydroxyandrost-4-ene-3,17-dione
C05290 19-Hydroxyandrost-4-ene-3,17-dione
C05291 7alpha-Hydroxytestosterone
C05293 5beta-Dihydrotestosterone
C05296 7alpha-Hydroxyandrost-4-ene-3,17-dione
C05297 19-Oxoandrost-4-ene-3,17-dione
C05302 2-Methoxy-17beta-estradiol
C05469 17alpha,21-Dihydroxy-5beta-pregnane-3,11,20-trione
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
C05483 3alpha,20alpha,21-Trihydroxy-5beta-pregnan-11-one
C05487 17alpha,21-Dihydroxypregnenolone
C05489 11beta,17alpha,21-Trihydroxypregnenolone
C05490 11-Dehydrocorticosterone
C05498 11beta-Hydroxyprogesterone
C05499 17alpha,20alpha-Dihydroxycholesterol
C05500 20alpha-Hydroxycholesterol
C05501 20alpha,22beta-Dihydroxycholesterol
C05502 22(R)-Hydroxycholesterol
C05503 Estradiol-17beta 3-glucuronide
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
C11134 Testosterone glucuronide
C11135 Androsterone glucuronide
C11136 Etiocholan-3alpha-ol-17-one 3-glucuronide
C13713 Allotetrahydrodeoxycorticosterone
C18038 7alpha-Hydroxypregnenolone
C18040 5alpha-Dihydrodeoxycorticosterone
C18041 5alpha-Pregnan-20alpha-ol-3-one
C18042 5alpha-Pregnane-3alpha,20alpha-diol
C18044 3beta-Hydroxypregn-5-en-20-one sulfate
C18045 7alpha-Hydroxydehydroepiandrosterone
C18075 11beta,17beta-Dihydroxy-4-androsten-3-one
C22831 5alpha-Pregnan-17alpha-ol-3,20-dione
C22832 5alpha-Pregnane-3alpha,17alpha-diol-20-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
Reference
Authors
Tomlinson JW, Stewart PM
Title
Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase.
Journal
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
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
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
Reference
Authors
Holmes MC, Seckl JR
Title
The role of 11beta-hydroxysteroid dehydrogenases in the brain.
Journal
Reference
Authors
Matsunaga T, Shintani S, Hara A
Title
Multiplicity of mammalian reductases for xenobiotic carbonyl compounds.
Journal
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
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
Reference
Authors
Ghayee HK, Auchus RJ
Title
Basic concepts and recent developments in human steroid hormone biosynthesis.
Journal
Related pathway
KO pathway
LinkDB
All DBs