Alternative pathway of fetal androgen synthesis (WP4524)

The development of sexual organs in humans is still not completely understood at the molecular level, controlled through the chromosomal difference between men and women. Steroids related to sexual development can have a temporary or permanent effects. Androgens are the leading compounds differentiating between (among other sexual organs) the internal and external genitalia of men. Next to the classical pathway of androgen synthesis (see []), alternative pathways are known, which make use of either selective expression patterns of isoenzymes or alternate enzymes. As an alternative, a socalled 'backdoor pathway', which can create dihydrotestosterone (DHT), skipping testosterone. Several enzymes between the classical and backdoor pathway are shared, however the later one utilises one unique enzyme, 3-alpha hydroxysteroid dehydrogenase 3 (gene: AKR1C2). Even though the relevance of this backdoor pathway for humans is not completely clear yet, mutations in the human AKR1C2 gene can lead to disordered sexual differentiation. This finding would indicate that both the classical and the alternative pathway are needed for normal development of male genitalia in humans. For more information on androgens, see Hiort (2013 []), and for more information on the disease linked to this pathway, please visit Chapter 37 of the book of Blau (ISBN 3642403360 (978-3642403361)).
last edited


ElineSanders, DeSl, Egonw, IreneHemel, MaintBot, Fehrhart, Eweitz, and Finterly

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Homo sapiens


Inborn Errors of Metabolism (IEM) Pathways Rare Diseases


Pathway Ontology: testosterone biosynthetic pathway altered steroid biosynthetic pathway steroid hormone metabolic pathway steroid metabolic pathway altered isoprenoid biosynthetic pathway cholesterol metabolic pathway steroid hormone biosynthetic pathway disease pathway

Disease Ontology: steroid inherited metabolic disorder


Label Type Compact Identifier
Dihydrotestosterone (DHT) Metabolite chebi:16330
Pregnenolone Metabolite chebi:16581
Androsterone Metabolite chebi:16032
17-Hydroxyallopregnanolone Metabolite chebi:11909
P450scc GeneProduct ensembl:ENSG00000140459
DHEA Metabolite chebi:28689
17-Hydroxypregnenolone Metabolite wikidata:Q2064889
Cytb5 Protein uniprot:P00167
3 HSD Protein uniprot:P26439
STAR GeneProduct ensembl:ENSG00000147465
AKR1C2 Protein uniprot:P52895
5-alpha-reductase 1 GeneProduct ensembl:ENSG00000277893
17-Hydroxyprogesterone Metabolite hmdb:HMDB0000374
P450c17 Protein ensembl:ENSG00000148795
NADP+ Metabolite chebi:58349
17-hydroxydihydroprogesterone Metabolite chebi:36723
NADPH Metabolite chebi:57783
RODH Protein uniprot:O14756
17-beta-HSD GeneProduct ensembl:ENSG00000130948
3-beta-HSD GeneProduct ensembl:ENSG00000203859
Androstanedione Metabolite chebi:15994
Androstenedione Metabolite chebi:16422
androst-4-ene-3,17-dione Metabolite chebi:16422
Progesterone Metabolite chebi:17026
AKR1C2/4 GeneProduct ensembl:ENSG00000151632
POR Protein uniprot:P16435
Cholesterol Metabolite chebi:16113
AKR1C4 GeneProduct ensembl:ENSG00000198610
NAD+ Metabolite chebi:57540
Testosterone Metabolite chebi:17347
Androstanediol Metabolite chebi:27727
POR Protein uniprot:P16435
P450c17 GeneProduct ensembl:ENSG00000148795
3-beta-HSD GeneProduct ensembl:ENSG00000203859
17-beta-HSD3 GeneProduct ensembl:ENSG00000130948
5-alpha-reductase 2 Protein uniprot:P31213
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein uniprot:P05093
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein ensembl:ENSG00000148795
POR Protein uniprot:P16435
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein ensembl:ENSG00000148795
POR Protein uniprot:P16435
P450c17 Protein ensembl:ENSG00000148795
P450c17 Protein ensembl:ENSG00000148795
POR Protein uniprot:P16435
POR Protein uniprot:P16435
NADH Metabolite chebi:57945
NADP+ Metabolite chebi:58349
NADPH Metabolite chebi:57783
NAD+ Metabolite chebi:57540
NADH Metabolite chebi:57945
AKR1C2 Protein uniprot:P52895


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