Entry 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. 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 metabolismBRITE hierarchy
Pathway map Module hsa_M00107 Steroid hormone biosynthesis, cholesterol => pregnenolone => 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 ]
hsa_M00976 C19-Steroid hormone biosynthesis, pregnenolone => testosterone => dihydrotestosterone [PATH:hsa00140 ]
hsa_M00977 C19-Steroid hormone biosynthesis (androgen backdoor pathway), pregnenolone => androsterone => dihydrotestosterone [PATH:hsa00140 ]
Network nt06019 Steroid hormone biosynthesis
Element N00338 Steroid hormone biosynthesis, progesterone to cortisol/cortisone
N00339 Steroid hormone biosynthesis, progesterone to aldosterone
N00759 Steroid hormone biosynthesis, cholesterol to pregnenolone/progesterone
N01541 Testosterone biosynthesis
N01802 Dihydrotestosterone biosynthesis
Drug D00156 Glycyrrhetinic acid (JAN)
D00321 Finasteride (JAN/USP/INN)
D00351 Ketoconazole (JP19/USP)
D00410 Metyrapone (JP19/USP/INN)
D00574 Aminoglutethimide (USP/INN)
D00960 Anastrozole (JP19/USP/INN)
D00963 Exemestane (JAN/USP/INN)
D00964 Letrozole (JAN/USP/INN)
D01134 Epristeride (JAN/USAN/INN)
D01899 Carbenoxolone sodium (JAN/USAN)
D02028 Diammonium glycyrrhizinate (JAN)
D02264 Dipotassium glycyrrhizinate (JAN)
D02451 Fadrozole hydrochloride (USAN)
D03107 Bexlosteride (USAN/INN)
D03778 Fadrozole hydrochloride hydrate (JAN)
D03781 Liarozole fumarate (USAN)
D03784 Liarozole hydrochloride (USAN)
D03820 Dutasteride (JAN/USP/INN)
D04987 Monoammonium glycyrrhizinate (JAN)
D05019 Metyrapone tartrate (USAN)
D08369 Polyphloroglucinol phosphate
D09701 Abiraterone acetate (JAN/USP)
D10950 Levoketoconazole (USAN/INN)
D11061 Osilodrostat (USAN/INN)
D11062 Osilodrostat phosphate (JAN/USAN)
D12773 Lorundrostat (USAN/INN)
D12774 Lorundrostat hydrobromide (USAN)
D12789 Baxdrostat (JAN/USAN/INN)
D13078 Linustedastat (USAN/INN)
D13111 Opevesostat tosylate (USAN)
D13200 Emestedastat (USAN/INN)
Other DBs Organism Homo sapiens (human) [GN:
hsa ]
Gene 10170 DHRS9; dehydrogenase/reductase SDR family member 9 isoform 1 precursor [KO:K11149 ] [EC:1.1.1.-]
1571 CYP2E1; cytochrome P450 2E1 [KO:K07415 ] [EC:1.14.14.-]
1583 CYP11A1; cholesterol side-chain cleavage enzyme, mitochondrial isoform a precursor [KO:K00498 ] [EC:1.14.15.6 ]
1584 CYP11B1; cytochrome P450 11B1, mitochondrial isoform 1 precursor [KO:K00497 ] [EC:1.14.15.4 ]
3291 HSD11B2; 11-beta-hydroxysteroid dehydrogenase type 2 [KO:K00071 ] [EC:1.1.1.-]
3292 HSD17B1; 17-beta-hydroxysteroid dehydrogenase type 1 isoform 1 [KO:K00044 ] [EC:1.1.1.62 ]
374875 HSD11B1L; hydroxysteroid 11-beta-dehydrogenase 1-like protein isoform e precursor [KO:K15680 ] [EC:1.1.1.146 ]
51170 HSD17B11; estradiol 17-beta-dehydrogenase 11 precursor [KO:K25779 ]
574537 UGT2A2; UDP-glucuronosyltransferase 2A2 isoform UGT2A2_i1 precursor [KO:K00699 ] [EC:2.4.1.17 ]
6718 AKR1D1; aldo-keto reductase family 1 member D1 isoform 1 [KO:K00251 ] [EC:1.3.1.3 ]
7363 UGT2B4; UDP-glucuronosyltransferase 2B4 isoform 1 precursor [KO:K00699 ] [EC:2.4.1.17 ]
7364 UGT2B7; UDP-glucuronosyltransferase 2B7 isoform 1 precursor [KO:K00699 ] [EC:2.4.1.17 ]
7365 UGT2B10; UDP-glucuronosyltransferase 2B10 isoform 1 precursor [KO:K00699 ] [EC:2.4.1.17 ]
79154 DHRS11; dehydrogenase/reductase SDR family member 11 precursor [KO:K22970 ]
Compound C00674 5alpha-Androstane-3,17-dione
C01124 18-Hydroxycorticosterone
C01176 17alpha-Hydroxyprogesterone
C03681 5alpha-Pregnane-3,20-dione
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 KO pathway
