Sex Hormone Biosynthesis

Pathway ID: SIGNOR-SHB

Description: The sex Hormone Biosynthetic pathway (also called Steroidogenesis) is an enzymatic cascade by which cholesterol is converted to biologically active steroid hormones. The first (rate-limiting) enzymatic step consists in the conversion of cholesterol into pregnenolone by P450 side chain cleavage (CYP11A1). Pregnenolone can subsequently be converted into progesterone by 3-beta-hydroxysteroid dehydrogenase (HSD3B1 and HSD3B2) or into 17-hydroxypregnenolone by 17-alpha-hydroxylase/17,20 lyase (CYP17A1). Then, CYP17A1 can convert progesterone into 17-hydroxyprogesterone, whereas HSD3B1 can convert 17-hydroxypregnenolone into 17-hydroxyprogesterone. In a next step, 17-hydroxypregnenolone and 17-hydroxyprogesterone can be converted by CYP17A1 into dehydroepiandrosterone (DHEA) and androstenedione, respectively. In turn, the activity of different 17beta-HSD enzymes catalyzes the synthesis of androstenediol from DHEA and testosterone from androstenedione. Aromatase converts androstenedione and testosterone into estrone and beta-estradiol, respectively. Considering glucocorticoids, the synthesis of 11-deoxycortisol and 11-deoxycorticosterone from 17-hydroxyprogesterone and progesterone, respectively, are catalyzed by 21-hydroxylase (CYP21A2), followed by the P450C11 (CYP11B1 and CYP11B2) activity leading to the synthesis of cortisol and corticosterone.

Curated by: Livia Perfetto

27 Seed Entities

Organism:
Name Primary ID
HSD3B1 P14060
CYP11B2 P19099
CYP17A1 P05093
cholesterol CHEBI:16113
STAR P49675
18-hydroxycorticosterone CHEBI:16485
androst-4-ene-3,17-dione CHEBI:16422
pregnenolone CHEBI:16581
11-deoxycortisol CHEBI:28324
testosterone CHEBI:17347
CYP19A1 P11511
HSD17B11 Q8NBQ5
CYP11A1 P05108
dehydroepiandrosterone CHEBI:28689
CYP11B1 P15538
cortisol CHEBI:17650
progesterone CHEBI:17026
androst-5-ene-3beta,17beta-diol CHEBI:2710
corticosterone CHEBI:16827
11-deoxycorticosterone CHEBI:16973
aldosterone CHEBI:27584
17alpha-hydroxyprogesterone CHEBI:17252
17beta-estradiol CHEBI:16469
HSD3B2 P26439
17alpha-hydroxypregnenolone CHEBI:28750
CYP21A2 P08686
estrone CHEBI:17263