KEGG   PATHWAY: hsa00140Help
Entry
hsa00140                    Pathway                                

Name
Steroid hormone biosynthesis - Homo sapiens (human)
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
Steroid hormone biosynthesis
hsa00140

All organismsOrtholog table
Module
Steroid hormone biosynthesis, cholesterol => prognenolone => progesterone [PATH:hsa00140]
C21-Steroid hormone biosynthesis, progesterone => corticosterone/aldosterone [PATH:hsa00140]
C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone [PATH:hsa00140]
C19/C18-Steroid hormone biosynthesis, pregnenolone => androstenedione => estrone [PATH:hsa00140]
Disease
H00134  
X-linked ichthyosis (XLI)
H00216  
Congenital adrenal hyperplasia (CAH)
H00258  
Aldosterone synthase deficiency
H00259  
Apparent mineralocorticoid excess syndrome
H00599  
46,XX disorders of sex development (Disorders related to androgen excess)
H00602  
Glucocorticoid-remediable aldosteronism (GRA)
H00608  
46,XY disorders of sex development (Disorders in androgen synthesis or action)
H00628  
Congenital bile acid synthesis defect (CBAS)
H00794  
Aromatase excess syndrome
H01075  
Peters anomaly
H01111  
Cortisone reductase deficiency (CRD)
H01203  
Primary congenital glaucoma (PCG)
Drug
D00152  
Phloroglucinol (JAN)
D00153  
Testolactone (USP/INN)
D00156  
Glycyrrhetinic acid (JAN)
D00321  
Finasteride (JAN/USP/INN)
D00351  
Ketoconazole (JP16/USP)
D00410  
Metyrapone (JP16/USP/INN)
D00420  
Mitotane (JAN/USP/INN)
D00574  
Aminoglutethimide (USP/INN)
D00781  
Entacapone (JAN/USAN/INN)
D00786  
Tolcapone (JAN/USAN/INN)
D00960  
Anastrozole (JAN/USAN/INN)
D00963  
Exemestane (JAN/USP/INN)
D00964  
Letrozole (JAN/USP/INN)
D01134  
Epristeride (JAN/USAN/INN)
D01180  
Trilostane (JAN/USAN)
D01259  
Flopropione (JP16/INN)
D01899  
Carbenoxolone sodium (JAN/USAN)
D02451  
Fadrozole hydrochloride (USAN)
D03107  
Bexlosteride (USAN/INN)
D03241  
Nitecapone (INN)
D03749  
Plomestane (USAN/INN)
D03778  
Fadrozole hydrochloride hydrate (JAN)
D03781  
Liarozole fumarate (USAN)
D03784  
Liarozole hydrochloride (USAN)
D03786  
Vorozole (USAN/INN)
D03820  
Dutasteride (JAN/USAN/INN)
D04035  
Epostane (USAN/INN)
D04498  
Idronoxil (USAN/INN)
D05019  
Metyrapone tartrate (USAN)
D07260  
Formestane (INN)
D07615  
Carbenoxolone (INN)
D07940  
Fadrozole (INN)
D08369  
Polyphloroglucinol phosphate
D09701  
Abiraterone acetate (JAN/USAN)
D09915  
Irosustat (USAN/INN)
D10125  
Galeterone (USAN)
D10146  
Orteronel (JAN/USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
1583  
CYP11A1; cytochrome P450, family 11, subfamily A, polypeptide 1 [KO:K00498] [EC:1.14.15.6]
1586  
CYP17A1; cytochrome P450, family 17, subfamily A, polypeptide 1 [KO:K00512] [EC:4.1.2.30 1.14.99.9]
412  
STS; steroid sulfatase (microsomal), isozyme S [KO:K01131] [EC:3.1.6.2]
6820  
SULT2B1; sulfotransferase family, cytosolic, 2B, member 1 [KO:K01015] [EC:2.8.2.2]
1589  
CYP21A2; cytochrome P450, family 21, subfamily A, polypeptide 2 [KO:K00513] [EC:1.14.99.10]
3283  
HSD3B1; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 [KO:K00070] [EC:5.3.3.1 1.1.1.145]
3284  
HSD3B2; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [KO:K00070] [EC:5.3.3.1 1.1.1.145]
6715  
SRD5A1; steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1) [KO:K12343] [EC:1.3.1.22]
6716  
SRD5A2; steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2) [KO:K12344] [EC:1.3.1.22]
79644  
SRD5A3; steroid 5 alpha-reductase 3 [KO:K12345] [EC:1.3.1.94 1.3.1.22]
1646  
AKR1C2; aldo-keto reductase family 1, member C2 [KO:K00089 K00212] [EC:1.1.1.213 1.3.1.20]
1109  
AKR1C4; aldo-keto reductase family 1, member C4 [KO:K00037 K00089 K00092 K00212] [EC:1.1.1.50 1.1.1.213 1.1.1.225 1.3.1.20]
1645  
AKR1C1; aldo-keto reductase family 1, member C1 [KO:K00089 K00212] [EC:1.1.1.213 1.3.1.20]
8644  
AKR1C3; aldo-keto reductase family 1, member C3 [KO:K04119] [EC:1.1.1.213 1.1.1.188 1.1.1.64]
1584  
CYP11B1; cytochrome P450, family 11, subfamily B, polypeptide 1 [KO:K00497] [EC:1.14.15.4]
1585  
CYP11B2; cytochrome P450, family 11, subfamily B, polypeptide 2 [KO:K07433] [EC:1.14.15.5 1.14.15.4]
6718  
AKR1D1; aldo-keto reductase family 1, member D1 [KO:K00251] [EC:1.3.1.3]
3290  
HSD11B1; hydroxysteroid (11-beta) dehydrogenase 1 [KO:K15680] [EC:1.1.1.146]
3291  
HSD11B2; hydroxysteroid (11-beta) dehydrogenase 2 [KO:K00071] [EC:1.1.1.-]
9420  
CYP7B1; cytochrome P450, family 7, subfamily B, polypeptide 1 [KO:K07430] [EC:1.14.13.100]
6783  
SULT1E1; sulfotransferase family 1E, estrogen-preferring, member 1 [KO:K01016] [EC:2.8.2.4]
3292  
HSD17B1; hydroxysteroid (17-beta) dehydrogenase 1 [KO:K00044] [EC:1.1.1.62]
3294  
HSD17B2; hydroxysteroid (17-beta) dehydrogenase 2 [KO:K13368] [EC:1.1.1.239 1.1.1.62]
8630  
HSD17B6; hydroxysteroid (17-beta) dehydrogenase 6 [KO:K13369] [EC:1.1.1.239 1.1.1.105 1.1.1.62]
51478  
HSD17B7; hydroxysteroid (17-beta) dehydrogenase 7 [KO:K13373] [EC:1.1.1.270 1.1.1.62]
7923  
HSD17B8; hydroxysteroid (17-beta) dehydrogenase 8 [KO:K13370] [EC:1.1.1.239 1.1.1.62]
51144  
HSD17B12; hydroxysteroid (17-beta) dehydrogenase 12 [KO:K10251] [EC:1.1.1.330 1.1.1.62]
1543  
CYP1A1; cytochrome P450, family 1, subfamily A, polypeptide 1 [KO:K07408] [EC:1.14.14.1]
1544  
CYP1A2; cytochrome P450, family 1, subfamily A, polypeptide 2 [KO:K07409] [EC:1.14.14.1]
1577  
CYP3A5; cytochrome P450, family 3, subfamily A, polypeptide 5 [KO:K17690] [EC:1.14.14.1]
1551  
CYP3A7; cytochrome P450, family 3, subfamily A, polypeptide 7 [KO:K17691] [EC:1.14.14.1]
1571  
CYP2E1; cytochrome P450, family 2, subfamily E, polypeptide 1 [KO:K07415] [EC:1.14.13.-]
1576  
CYP3A4; cytochrome P450, family 3, subfamily A, polypeptide 4 [KO:K17689] [EC:1.14.13.- 1.14.13.157 1.14.13.97 1.14.13.67 1.14.13.32]
1545  
CYP1B1; cytochrome P450, family 1, subfamily B, polypeptide 1 [KO:K07410] [EC:1.14.14.1]
1588  
CYP19A1; cytochrome P450, family 19, subfamily A, polypeptide 1 [KO:K07434] [EC:1.14.14.14]
1581  
CYP7A1; cytochrome P450, family 7, subfamily A, polypeptide 1 [KO:K00489] [EC:1.14.13.17]
10941  
UGT2A1; UDP glucuronosyltransferase 2 family, polypeptide A1, complex locus [KO:K00699] [EC:2.4.1.17]
79799  
UGT2A3; UDP glucuronosyltransferase 2 family, polypeptide A3 [KO:K00699] [EC:2.4.1.17]
7367  
UGT2B17; UDP glucuronosyltransferase 2 family, polypeptide B17 [KO:K00699] [EC:2.4.1.17]
10720  
UGT2B11; UDP glucuronosyltransferase 2 family, polypeptide B11 [KO:K00699] [EC:2.4.1.17]
54490  
UGT2B28; UDP glucuronosyltransferase 2 family, polypeptide B28 [KO:K00699] [EC:2.4.1.17]
54578  
UGT1A6; UDP glucuronosyltransferase 1 family, polypeptide A6 [KO:K00699] [EC:2.4.1.17]
54657  
UGT1A4; UDP glucuronosyltransferase 1 family, polypeptide A4 [KO:K00699] [EC:2.4.1.17]
54658  
UGT1A1; UDP glucuronosyltransferase 1 family, polypeptide A1 [KO:K00699] [EC:2.4.1.17]
54659  
UGT1A3; UDP glucuronosyltransferase 1 family, polypeptide A3 [KO:K00699] [EC:2.4.1.17]
7365  
UGT2B10; UDP glucuronosyltransferase 2 family, polypeptide B10 [KO:K00699] [EC:2.4.1.17]
54600  
UGT1A9; UDP glucuronosyltransferase 1 family, polypeptide A9 [KO:K00699] [EC:2.4.1.17]
7364  
UGT2B7; UDP glucuronosyltransferase 2 family, polypeptide B7 [KO:K00699] [EC:2.4.1.17]
54575  
UGT1A10; UDP glucuronosyltransferase 1 family, polypeptide A10 [KO:K00699] [EC:2.4.1.17]
54576  
UGT1A8; UDP glucuronosyltransferase 1 family, polypeptide A8 [KO:K00699] [EC:2.4.1.17]
54579  
UGT1A5; UDP glucuronosyltransferase 1 family, polypeptide A5 [KO:K00699] [EC:2.4.1.17]
7366  
UGT2B15; UDP glucuronosyltransferase 2 family, polypeptide B15 [KO:K00699] [EC:2.4.1.17]
54577  
UGT1A7; UDP glucuronosyltransferase 1 family, polypeptide A7 [KO:K00699] [EC:2.4.1.17]
7363  
UGT2B4; UDP glucuronosyltransferase 2 family, polypeptide B4 [KO:K00699] [EC:2.4.1.17]
574537  
UGT2A2; UDP glucuronosyltransferase 2 family, polypeptide A2 [KO:K00699] [EC:2.4.1.17]
1312  
COMT; catechol-O-methyltransferase [KO:K00545] [EC:2.1.1.6]
3293  
HSD17B3; hydroxysteroid (17-beta) dehydrogenase 3 [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)
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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