Biomaterial Database

AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders. 2019

Trevor M Penning

Department of Systems Pharmacology and Translational Therapeutics and Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 1315 BRBII/III 421 Curie Blvd, Philadelphia, PA, 19104, USA. Electronic address: penning@upenn.edu.

Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F2α synthase) is the only 17β-HSD that is not a short-chain dehydrogenase/reductase. By acting as a 17-ketosteroid reductase, AKR1C3 produces potent androgens in peripheral tissues which activate the androgen receptor (AR) or act as substrates for aromatase. AKR1C3 is implicated in the production of androgens in castration-resistant prostate cancer (CRPC) and polycystic ovarian syndrome; and is implicated in the production of aromatase substrates in breast cancer. By acting as an 11-ketoprostaglandin reductase, AKR1C3 generates 11β-PGF2α to activate the FP receptor and deprives peroxisome proliferator activator receptorγ of its putative PGJ2 ligands. These growth stimulatory signals implicate AKR1C3 in non-hormonal dependent malignancies e.g. acute myeloid leukemia (AML). AKR1C3 moonlights by acting as a co-activator of the AR and stabilizes ubiquitin ligases. AKR1C3 inhibitors have been used clinically for CRPC and AML and can be used to probe its pluripotency.

UI	MeSH Term	Description	Entries
D004700	Endocrine System Diseases	Pathological processes of the ENDOCRINE GLANDS, and diseases resulting from abnormal level of available HORMONES.	Endocrine Diseases,Diseases of Endocrine System,Disease, Endocrine,Disease, Endocrine System,Diseases, Endocrine,Diseases, Endocrine System,Endocrine Disease,Endocrine System Disease,System Disease, Endocrine,System Diseases, Endocrine
D004701	Endocrine Gland Neoplasms	Tumors or cancer of the ENDOCRINE GLANDS.	Cancer of Endocrine Gland,Endocrine Cancer,Endocrine Gland Cancer,Cancer of the Endocrine Gland,Carcinoma of Endocrine Gland,Endocrine Gland Carcinoma,Neoplasms, Endocrine Gland,Cancer, Endocrine,Cancer, Endocrine Gland,Cancers, Endocrine,Carcinoma, Endocrine Gland,Endocrine Cancers,Endocrine Gland Neoplasm,Neoplasm, Endocrine Gland
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074425	Aldo-Keto Reductase Family 1 Member C3	Aldo-keto reductase that functions as a bi-directional 17 BETA, 20 ALPHA-HYDROXYSTEROID DEHYDROGENASE. It catalyzes the reduction of PROSTAGLANDIN D2 and PROSTAGLANDIN H2, as well as the oxidation of 9alpha,11beta-PGF2 to prostaglandin D2. It can also interconvert estrogens, ANDROGENS; and PROGESTINS between their active forms and inactive metabolites.	17-beta-Hydroxysteroid Dehydrogenase Type 5,AKR1C3 Protein,Dihydrodiol Dehydrogenase 3,17 beta Hydroxysteroid Dehydrogenase Type 5,Aldo Keto Reductase Family 1 Member C3
D013256	Steroids	A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)	Steroid,Catatoxic Steroids,Steroids, Catatoxic
D044127	Epigenesis, Genetic	A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.	Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics