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. 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 hsa00140 Steroid hormone biosynthesis 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 N00309 Cortisone reduction N00338 Steroid hormone biosynthesis, progesterone to cortisol/cortisone N00339 Steroid hormone biosynthesis, progesterone to aldosterone N00759 Steroid hormone biosynthesis, cholesterol to pregnenolone/progesterone N01540 Estrogen biosynthesis N01541 Testosterone biosynthesis N01802 Dihydrotestosterone biosynthesis DRUG D00152 Phloroglucinol (JAN) D00153 Testolactone (USP/INN) D00156 Glycyrrhetinic acid (JAN) D00321 Finasteride (JAN/USP/INN) D00351 Ketoconazole (JP19/USP) D00410 Metyrapone (JP19/USP/INN) D00420 Mitotane (JAN/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) D01180 Trilostane (JAN/USAN) D01259 Flopropione (JP19/INN) D01899 Carbenoxolone sodium (JAN/USAN) D02028 Diammonium glycyrrhizinate (JAN) D02264 Dipotassium glycyrrhizinate (JAN) 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/USP/INN) D04035 Epostane (USAN/INN) D04498 Idronoxil (USAN/INN) D04646 Izonsteride (USAN/INN) D04987 Monoammonium glycyrrhizinate (JAN) D05019 Metyrapone tartrate (USAN) D05746 Rogletimide (USAN/INN) D07121 Alfatradiol (INN) D07260 Formestane (INN) D07615 Carbenoxolone (INN) D07940 Fadrozole (INN) D08369 Polyphloroglucinol phosphate D09701 Abiraterone acetate (JAN/USP) D09915 Irosustat (USAN/INN) D10125 Galeterone (USAN) D10146 Orteronel (JAN/USAN) 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) D12948 Clofutriben (USAN/INN) D13078 Linustedastat (USAN/INN) D13110 Opevesostat (USAN/INN) D13111 Opevesostat tosylate (USAN) D13192 Vicadrostat (USAN/INN) D13200 Emestedastat (USAN/INN) DBLINKS GO: 0034754 ORGANISM Homo sapiens (human) [GN:hsa] GENE 100861540 CYP3A7-CYP3A51P; CYP3A7-CYP3A51P protein [KO:K17691] [EC:1.14.14.1] 10170 DHRS9; dehydrogenase/reductase SDR family member 9 isoform 1 precursor [KO:K11149] [EC:1.1.1.-] 10720 UGT2B11; UDP-glucuronosyltransferase 2B11 precursor [KO:K00699] [EC:2.4.1.17] 10941 UGT2A1; UDP-glucuronosyltransferase 2A1 isoform 3 precursor [KO:K00699] [EC:2.4.1.17] 1109 AKR1C4; aldo-keto reductase family 1 member C4 [KO:K00037] [EC:1.1.1.50 1.1.1.357 1.1.1.225] 120356740 TOMT; transmembrane O-methyltransferase [KO:K00545] [EC:2.1.1.6] 1312 COMT; catechol O-methyltransferase isoform MB-COMT [KO:K00545] [EC:2.1.1.6] 1543 CYP1A1; cytochrome P450 1A1 isoform 1 [KO:K07408] [EC:1.14.14.1] 1544 CYP1A2; cytochrome P450 1A2 [KO:K07409] [EC:1.14.14.1] 1545 CYP1B1; cytochrome P450 1B1 [KO:K07410] [EC:1.14.14.1] 1551 CYP3A7; cytochrome P450 3A7 [KO:K17691] [EC:1.14.14.1] 1571 CYP2E1; cytochrome P450 2E1 [KO:K07415] [EC:1.14.14.-] 1576 CYP3A4; cytochrome P450 3A4 isoform 1 [KO:K17689] [EC:1.14.13.32 1.14.14.55 1.14.14.56 1.14.14.57 1.14.14.73 1.14.14.-] 1577 CYP3A5; cytochrome P450 3A5 isoform 1 [KO:K17690] [EC:1.14.14.1] 1581 CYP7A1; cytochrome P450 7A1 [KO:K00489] [EC:1.14.14.23] 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] 1585 CYP11B2; cytochrome P450 11B2, mitochondrial precursor [KO:K07433] [EC:1.14.15.4 1.14.15.5] 1586 CYP17A1; steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32] 1588 CYP19A1; aromatase [KO:K07434] [EC:1.14.14.14] 1589 CYP21A2; steroid 21-hydroxylase isoform a [KO:K00513] [EC:1.14.14.16] 1645 AKR1C1; aldo-keto reductase family 1 member C1 [KO:K00212] [EC:1.1.1.149 1.1.1.357 1.3.1.20] 1646 AKR1C2; aldo-keto reductase family 1 member C2 isoform 1 [KO:K00089] [EC:1.1.1.213 1.1.1.357] 220074 LRTOMT; transmembrane O-methyltransferase isoform LRTOMT2a [KO:K00545] [EC:2.1.1.6] 3283 HSD3B1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1] 3284 HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1] 3290 HSD11B1; 11-beta-hydroxysteroid dehydrogenase 1 [KO:K15680] [EC:1.1.1.146] 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] 3293 HSD17B3; 17-beta-hydroxysteroid dehydrogenase type 3 [KO:K10207] [EC:1.1.1.64] 3294 HSD17B2; 17-beta-hydroxysteroid dehydrogenase type 2 [KO:K13368] [EC:1.1.1.62 1.1.1.239] 340811 AKR1C8; aldo-keto reductase family 1 member C8 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357] 374875 HSD11B1L; hydroxysteroid 11-beta-dehydrogenase 1-like protein isoform e precursor [KO:K15680] [EC:1.1.1.146] 412 STS; steryl-sulfatase isoform 1 precursor [KO:K01131] [EC:3.1.6.2] 51144 HSD17B12; very-long-chain 3-oxoacyl-CoA reductase [KO:K10251] [EC:1.1.1.62 1.1.1.330] 51170 HSD17B11; estradiol 17-beta-dehydrogenase 11 precursor [KO:K25779] 51478 HSD17B7; 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 isoform 1 [KO:K13373] [EC:1.1.1.62 1.1.1.270] 54490 UGT2B28; UDP-glucuronosyltransferase 2B28 isoform 1 precursor [KO:K00699] [EC:2.4.1.17] 54575 UGT1A10; UDP-glucuronosyltransferase 1A10 precursor [KO:K00699] [EC:2.4.1.17] 54576 UGT1A8; UDP-glucuronosyltransferase 1A8 precursor [KO:K00699] [EC:2.4.1.17] 54577 UGT1A7; UDP-glucuronosyltransferase 1A7 precursor [KO:K00699] [EC:2.4.1.17] 54578 UGT1A6; UDP-glucuronosyltransferase 1A6 isoform 1 precursor [KO:K00699] [EC:2.4.1.17] 54579 UGT1A5; UDP-glucuronosyltransferase 1A5 precursor [KO:K00699] [EC:2.4.1.17] 54600 UGT1A9; UDP-glucuronosyltransferase 1A9 precursor [KO:K00699] [EC:2.4.1.17] 54657 UGT1A4; UDP-glucuronosyltransferase 1A4 precursor [KO:K00699] [EC:2.4.1.17] 54658 UGT1A1; UDP-glucuronosyltransferase 1A1 precursor [KO:K00699] [EC:2.4.1.17] 54659 UGT1A3; UDP-glucuronosyltransferase 1A3 precursor [KO:K00699] [EC:2.4.1.17] 574537 UGT2A2; UDP-glucuronosyltransferase 2A2 isoform UGT2A2_i1 precursor [KO:K00699] [EC:2.4.1.17] 5959 RDH5; retinol dehydrogenase 5 [KO:K00061] [EC:1.1.1.315 1.1.1.-] 6715 SRD5A1; 3-oxo-5-alpha-steroid 4-dehydrogenase 1 isoform 1 [KO:K12343] [EC:1.3.1.22] 6716 SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22] 6718 AKR1D1; aldo-keto reductase family 1 member D1 isoform 1 [KO:K00251] [EC:1.3.1.3] 6783 SULT1E1; sulfotransferase 1E1 [KO:K01016] [EC:2.8.2.4] 6820 SULT2B1; sulfotransferase 2B1 isoform b [KO:K01015] [EC:2.8.2.2] 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] 7366 UGT2B15; UDP-glucuronosyltransferase 2B15 precursor [KO:K00699] [EC:2.4.1.17] 7367 UGT2B17; UDP-glucuronosyltransferase 2B17 precursor [KO:K00699] [EC:2.4.1.17] 79154 DHRS11; dehydrogenase/reductase SDR family member 11 precursor [KO:K22970] 7923 HSD17B8; (3R)-3-hydroxyacyl-CoA dehydrogenase [KO:K13370] [EC:1.1.1.62 1.1.1.239] 79644 SRD5A3; polyprenal reductase isoform 1 [KO:K12345] [EC:1.3.1.22 1.3.1.94] 79799 UGT2A3; UDP-glucuronosyltransferase 2A3 precursor [KO:K00699] [EC:2.4.1.17] 8630 HSD17B6; 17-beta-hydroxysteroid dehydrogenase type 6 precursor [KO:K13369] [EC:1.1.1.62 1.1.1.105 1.1.1.239] 8644 AKR1C3; aldo-keto reductase family 1 member C3 isoform 1 [KO:K04119] [EC:1.1.1.51 1.1.1.188 1.1.1.213 1.1.1.357] 9420 CYP7B1; cytochrome P450 7B1 isoform 1 [KO:K07430] [EC:1.14.14.29] 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 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 Dihydrocortisol 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 C22831 5alpha-Pregnan-17alpha-ol-3,20-dione C22832 5alpha-Pregnane-3alpha,17alpha-diol-20-one REFERENCE PMID:10998348 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 PMID:11469811 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 PMID:12604236 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 PMID:12832414 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 PMID:15642792 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 PMID:16413106 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 PMID:16547389 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 PMID:17459698 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 PMID:17475203 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 PMID:17926129 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 REL_PATHWAY hsa00100 Steroid biosynthesis KO_PATHWAY ko00140 ///