Classical pathway of steroidogenesis with glucocorticoid and mineralocorticoid metabolism (WP4523)

Homo sapiens

The biosynthesis of steroid hormones is a difficult process in which Cholesterol is transformed into mineralocorticoids, glucocorticoids and sex hormones via a series of hydroxylation, oxidation and reduction steps. To better understand the molecular level of sexual organ maturation in humans, the classical pathway and the alternative pathway of this process are produced. The pathways produce the main steroid hormones in humans, namely Progestogen, Corticosteroids, Androgens and Estrogens. The classical pathway is meant to produce an important steroid called Androgen, which is a synthetic steroid hormone that regulates sexual development and the maintenance of the male sex organs via binding to androgen receptors. Next to the classical pathway of androgen synthesis, alternative pathways are known, such as []. For more information and details about Androgens and the diseases linked with this molecular pathway, please visit Chapter 37 of the book of Blau (ISBN 3642403360 (978-3642403361)) . We have recently expanded this pathway with information from the Glucocorticoid and Mineralocorticoid Metabolism (previously captured in WP273; overlapping content is indicated with double borders for individual datanodes; information previously missing is added with dashed borders). Mineralocorticoid (M) and glucocorticoid (G) receptors regulate transcription; either through 11-beta-hydroxysteroid dehydrogenase influencing aldosterone specificity on epithelial M-receptors or by modulcation of AP-1- and NF-kappa-B-induced transcription through G-receptors. Specifically for the first case, aldosterone resistance in an autosomal form (aka pseudohypoaldosteronism) is linked to loss-of-function in epithelical Na-channel subunits [].
last edited


Eline Sanders , Ingebude , Denise Slenter , Irene Hemel , Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Finterly Hu

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Homo sapiens


Inborn Errors of Metabolism (IEM) Pathways Rare Diseases


Pathway Ontology: lipoid congenital adrenal hyperplasia pathway steroid biosynthetic pathway classic metabolic pathway apparent mineralocorticoid excess syndrome pathway C19-steroid hormone biosynthetic pathway C21-steroid hormone biosynthetic pathway congenital adrenal hyperplasia pathway disease pathway glucocorticoid biosynthetic pathway

Disease Ontology: congenital adrenal hyperplasia apparent mineralocorticoid excess syndrome cortisone reductase deficiency obsolete apparent mineralocorticoid excess pseudohermaphroditism congenital adrenal insufficiency


Label Type Compact Identifier Comment
Dihydrotestosterone Metabolite chebi:16330
Testosterone Metabolite chebi:17347
Oestradiol Metabolite chebi:16469
Cholesterol Metabolite chebi:16113
17-hydroxyprogesterone Metabolite chebi:17252
Cortisone Metabolite chebi:16962
Progesterone Metabolite chebi:17026
Corticosterone Metabolite chebi:16827
11-Deoxycortisol Metabolite chebi:28324
DHEA Metabolite chebi:28689
Cortisol Metabolite wikidata:Q190875
Androstenedione Metabolite chebi:16422
(11)-Deoxycorticosterone Metabolite chebi:16973
18-hydroxycorticosterone Metabolite chebi:16485
Aldosterone Metabolite chebi:27584
17-hydroxypregnenolone Metabolite chebi:28750
Pregnenolone Metabolite chebi:16581
NADP+ Metabolite chebi:58349
NADPH Metabolite chebi:57783
11b, 21-Dihydroxy-3,20-5b-Pregnan-18-al Metabolite pubchem.compound:44263338
3a,11b,21-Trihydroxy-20-Oxo-5b-Pregnan-18-al Metabolite pubchem.compound:44263346
3a-OH-5b-Pregnane-20-one Metabolite pubchem.compound:24779614
5b-Pregnane-3,20-dione Metabolite pubchem.compound:92745
Pregnanediol Metabolite cas:80-92-2
Glucuronides Metabolite chebi:26763
17a,21-Dihydroxy-5b-17a,21-Dihydroxy-5b-Pregnane-3,11,20-trione Metabolite pubchem.compound:65554 aka 4,5beta-Dihydrocortisone
Urocortisone Metabolite pubchem.compound:5754
Cortolone Metabolite cas:516-42-7
Urocortisol Metabolite pubchem.compound:5864 AKA Tetrahydrocortisol
11b,17a 21-Trihydroxy-5bPregnane 3,20-dione Metabolite cas:1482-50-4 AKA 11-BETA,17-ALPHA,21-TRIHYDROXY-5-BETA-PREGNANE-3,20-DIONE
Cortisol Metabolite wikidata:Q190875
CYP11A1 GeneProduct ncbigene:1583
HSD3B1 GeneProduct ncbigene:3283
HSD3B2 GeneProduct ncbigene:3284
CYP11B2 GeneProduct ncbigene:1585
Corticosterone Methyl Oxidase Protein ensembl:ENSG00000179142
P450scc Protein ensembl:ENSG00000140459 also known as CYP11A1
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P450c21 Protein ensembl:ENSG00000231852
11beta-HSD1 Protein ensembl:ENSG00000117594 Reference study in mice [PMID:9405715]
3-beta-HSD Protein ensembl:ENSG00000203859
STAR Protein ensembl:ENSG00000147465
11beta-HSD2 Protein ensembl:ENSG00000176387
POR Protein uniprot:P16435
POR Protein uniprot:P16435
17-beta-HSD3 Protein ensembl:ENSG00000130948
H6PD Protein ensembl:ENSG00000049239 This enzyme produces NADPH which is neccessary for 11beta-HSD1 to convert cortisone into cortisol.
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POR Protein uniprot:P16435
Cytochrome b5 Protein uniprot:J3KNC7
P450c17 Protein ensembl:ENSG00000148795
5-alpha-Reductase2 Protein ensembl:ENSG00000277893
P450Aro Protein ensembl:ENSG00000137869
3-beta-HSD Protein ensembl:ENSG00000203859
P450c11 Protein ensembl:ENSG00000160882
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein ensembl:ENSG00000148795
3-beta-HSD Protein ensembl:ENSG00000203859
POR Protein uniprot:P16435
HSD3B1 Protein ncbigene:3283
3B-OH-delta-Steroid Dh Protein eccode:
Corticosterone 18-Monooxy Protein eccode: EC number:
3-Oxo-5b-Steroid Dh Protein uniprot:3O5B
3a-Hydroxy-steroid Dh Protein eccode: SPs:DIDH RAT
20b-Hydroxy-steroid Dh Protein eccode:, similiar SP:2BHD STREX
Cortisone beta-reductase Protein eccode:
3a-Hydroxy-steroid Dh Protein eccode: SPs:DIDH RAT
(R)20-hydroxy-steroid Dh Protein eccode:, similiar SP:2BHD STREX


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