Steroid hormone biosynthesis - Homo sapiens (human)
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:
]. 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:
]. Cortisol, the main glucocorticoid, is formed from 17alpha-hydroxyprogesterone with 11-deoxycortisol as an intermediate [MD:
]. (ii) Male hormone testosterone is formed from pregnenolone by two pathways, delta5 pathway via dehydroepiandrosterone and delta4 pathway via androstenedione [MD:
]. 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:
]. 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.
Metabolism; Lipid metabolism
Pathway map Ortholog table
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]
Steroid hormone biosynthesis
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
D00156 Glycyrrhetinic acid (JAN)
D00321 Finasteride (JAN/USP/INN)
D00351 Ketoconazole (JP18/USP)
D00410 Metyrapone (JP18/USP/INN)
D00574 Aminoglutethimide (USP/INN)
D00960 Anastrozole (JP18/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)
Homo sapiens (human) [GN:
3291 HSD11B2; hydroxysteroid 11-beta dehydrogenase 2 [KO: K00071] [EC:1.1.1.-]
1571 CYP2E1; cytochrome P450 family 2 subfamily E member 1 [KO: K07415] [EC:1.14.14.-]
51170 HSD17B11; hydroxysteroid 17-beta dehydrogenase 11 [KO: K25779] [EC:1.1.1.-]
10941 UGT2A1; UDP glucuronosyltransferase family 2 member A1 complex locus [KO: K00699] [EC: 22.214.171.124]
220074 LRTOMT; leucine rich transmembrane and O-methyltransferase domain containing [KO: K00545] [EC: 126.96.36.199]
C04555 Dehydroepiandrosterone sulfate
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
C18044 3beta-Hydroxypregn-5-en-20-one sulfate
Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K
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.
Tomlinson JW, Stewart PM
Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase.
Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A
Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.
Thomas JL, Duax WL, Addlagatta A, Brandt S, Fuller RR, Norris W
Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1 3 beta-hydroxysteroid dehydrogenase/isomerase.
Cavigelli SA, Monfort SL, Whitney TK, Mechref YS, Novotny M, McClintock MK
Frequent serial fecal corticoid measures from rats reflect circadian and ovarian corticosterone rhythms.
Holmes MC, Seckl JR
The role of 11beta-hydroxysteroid dehydrogenases in the brain.
Matsunaga T, Shintani S, Hara A
Multiplicity of mammalian reductases for xenobiotic carbonyl compounds.
Morris DJ, Latif SA, Hardy MP, Brem AS
Endogenous inhibitors (GALFs) of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2: derivatives of adrenally produced corticosterone and cortisol.
Sanai M, Endo S, Matsunaga T, Ishikura S, Tajima K, El-Kabbani O, Hara A
Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.
Ghayee HK, Auchus RJ
Basic concepts and recent developments in human steroid hormone biosynthesis.