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Entry
map00140                    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
BRITE hierarchy
Pathway map
map00140  Steroid hormone biosynthesis
map00140

Ortholog table
Module
M00107  Steroid hormone biosynthesis, cholesterol => prognenolone => progesterone [PATH:map00140]
M00108  C21-Steroid hormone biosynthesis, progesterone => corticosterone/aldosterone [PATH:map00140]
M00109  C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone [PATH:map00140]
M00110  C19/C18-Steroid hormone biosynthesis, pregnenolone => androstenedione => estrone [PATH:map00140]
Disease
H00134  X-linked ichthyosis
H00216  Congenital adrenal hyperplasia
H00258  Aldosterone synthase deficiency
H00259  Apparent mineralocorticoid excess syndrome
H00602  Glucocorticoid-remediable aldosteronism (GRA)
H00608  46,XY disorder of sex development due to testosterone secretion defect
H00628  Congenital bile acid synthesis defect
H00794  Aromatase excess syndrome
H01111  Cortisone reductase deficiency
H01203  Primary congenital glaucoma
H01709  Glucocorticoid-induced osteonecrosis
H02020  Aromatase deficiency
H02314  Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete
Other DBs
GO: 0034754
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
map00100  Steroid biosynthesis
KO pathway
ko00140   
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