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
hsa00140  Steroid hormone biosynthesis
hsa00140

Ortholog table
Module
hsa_M00107  Steroid hormone biosynthesis, cholesterol => prognenolone => progesterone [PATH:hsa00140]
hsa_M00108  C21-Steroid hormone biosynthesis, progesterone => corticosterone/aldosterone [PATH:hsa00140]
hsa_M00109  C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone [PATH:hsa00140]
hsa_M00110  C19/C18-Steroid hormone biosynthesis, pregnenolone => androstenedione => estrone [PATH:hsa00140]
Network
N00309  Cortisone reduction
N00338  Cortisol biosynthesis
N00339  Aldosterone biosynthesis
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)
H01709  Glucocorticoid-induced osteonecrosis
H02020  Aromatase deficiency
Drug
D00152  Phloroglucinol (JAN)
D00153  Testolactone (USP/INN)
D00156  Glycyrrhetinic acid (JAN)
D00321  Finasteride (JAN/USP/INN)
D00351  Ketoconazole (JP17/USP)
D00410  Metyrapone (JP17/USP/INN)
D00420  Mitotane (JAN/USP/INN)
D00574  Aminoglutethimide (USP/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 (JP17/INN)
D01899  Carbenoxolone sodium (JAN/USAN)
D02451  Fadrozole hydrochloride (USAN)
D03107  Bexlosteride (USAN/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)
D04646  Izonsteride (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)
D11061  Osilodrostat (USAN/INN)
Other DBs
BSID: 82940
GO: 0034754
Organism
Homo sapiens (human) [GN:hsa]
Gene
1583  CYP11A1; cytochrome P450 family 11 subfamily A member 1 [KO:K00498] [EC:1.14.15.6]
1586  CYP17A1; cytochrome P450 family 17 subfamily A member 1 [KO:K00512] [EC:1.14.14.32 1.14.14.19]
412  STS; steroid sulfatase [KO:K01131] [EC:3.1.6.2]
6820  SULT2B1; sulfotransferase family 2B member 1 [KO:K01015] [EC:2.8.2.2]
1589  CYP21A2; cytochrome P450 family 21 subfamily A member 2 [KO:K00513] [EC:1.14.14.16]
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 1 [KO:K12343] [EC:1.3.1.22]
6716  SRD5A2; steroid 5 alpha-reductase 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] [EC:1.1.1.357 1.1.1.213]
8644  AKR1C3; aldo-keto reductase family 1 member C3 [KO:K04119] [EC:1.1.1.357 1.1.1.213 1.1.1.188 1.1.1.51]
1584  CYP11B1; cytochrome P450 family 11 subfamily B member 1 [KO:K00497] [EC:1.14.15.4]
1585  CYP11B2; cytochrome P450 family 11 subfamily B member 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]
1109  AKR1C4; aldo-keto reductase family 1 member C4 [KO:K00037] [EC:1.1.1.225 1.1.1.357 1.1.1.50]
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.-]
1645  AKR1C1; aldo-keto reductase family 1 member C1 [KO:K00212] [EC:1.3.1.20 1.1.1.357 1.1.1.149]
9420  CYP7B1; cytochrome P450 family 7 subfamily B member 1 [KO:K07430] [EC:1.14.14.29]
6783  SULT1E1; sulfotransferase family 1E 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 member 1 [KO:K07408] [EC:1.14.14.1]
1544  CYP1A2; cytochrome P450 family 1 subfamily A member 2 [KO:K07409] [EC:1.14.14.1]
1577  CYP3A5; cytochrome P450 family 3 subfamily A member 5 [KO:K17690] [EC:1.14.14.1]
1551  CYP3A7; cytochrome P450 family 3 subfamily A member 7 [KO:K17691] [EC:1.14.14.1]
100861540  CYP3A7-CYP3A51P; CYP3A7-CYP3A51P readthrough [KO:K17691] [EC:1.14.14.1]
1571  CYP2E1; cytochrome P450 family 2 subfamily E member 1 [KO:K07415] [EC:1.14.13.-]
1576  CYP3A4; cytochrome P450 family 3 subfamily A member 4 [KO:K17689] [EC:1.14.13.- 1.14.14.57 1.14.14.56 1.14.14.55 1.14.13.32]
1545  CYP1B1; cytochrome P450 family 1 subfamily B member 1 [KO:K07410] [EC:1.14.14.1]
1588  CYP19A1; cytochrome P450 family 19 subfamily A member 1 [KO:K07434] [EC:1.14.14.14]
1581  CYP7A1; cytochrome P450 family 7 subfamily A member 1 [KO:K00489] [EC:1.14.14.23]
10941  UGT2A1; UDP glucuronosyltransferase family 2 member A1 complex locus [KO:K00699] [EC:2.4.1.17]
79799  UGT2A3; UDP glucuronosyltransferase family 2 member A3 [KO:K00699] [EC:2.4.1.17]
7367  UGT2B17; UDP glucuronosyltransferase family 2 member B17 [KO:K00699] [EC:2.4.1.17]
10720  UGT2B11; UDP glucuronosyltransferase family 2 member B11 [KO:K00699] [EC:2.4.1.17]
54490  UGT2B28; UDP glucuronosyltransferase family 2 member B28 [KO:K00699] [EC:2.4.1.17]
54578  UGT1A6; UDP glucuronosyltransferase family 1 member A6 [KO:K00699] [EC:2.4.1.17]
54657  UGT1A4; UDP glucuronosyltransferase family 1 member A4 [KO:K00699] [EC:2.4.1.17]
54658  UGT1A1; UDP glucuronosyltransferase family 1 member A1 [KO:K00699] [EC:2.4.1.17]
54659  UGT1A3; UDP glucuronosyltransferase family 1 member A3 [KO:K00699] [EC:2.4.1.17]
7365  UGT2B10; UDP glucuronosyltransferase family 2 member B10 [KO:K00699] [EC:2.4.1.17]
54600  UGT1A9; UDP glucuronosyltransferase family 1 member A9 [KO:K00699] [EC:2.4.1.17]
7364  UGT2B7; UDP glucuronosyltransferase family 2 member B7 [KO:K00699] [EC:2.4.1.17]
54575  UGT1A10; UDP glucuronosyltransferase family 1 member A10 [KO:K00699] [EC:2.4.1.17]
54576  UGT1A8; UDP glucuronosyltransferase family 1 member A8 [KO:K00699] [EC:2.4.1.17]
54579  UGT1A5; UDP glucuronosyltransferase family 1 member A5 [KO:K00699] [EC:2.4.1.17]
7366  UGT2B15; UDP glucuronosyltransferase family 2 member B15 [KO:K00699] [EC:2.4.1.17]
54577  UGT1A7; UDP glucuronosyltransferase family 1 member A7 [KO:K00699] [EC:2.4.1.17]
7363  UGT2B4; UDP glucuronosyltransferase family 2 member B4 [KO:K00699] [EC:2.4.1.17]
574537  UGT2A2; UDP glucuronosyltransferase family 2 member A2 [KO:K00699] [EC:2.4.1.17]
1312  COMT; catechol-O-methyltransferase [KO:K00545] [EC:2.1.1.6]
220074  LRTOMT; leucine rich transmembrane and O-methyltransferase domain containing [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)
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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