Synonyms: 17bHSD2, HSD17B2, 17b-HSD2, 17ß-HSD2, 17beta-HSOR Type 2, 17b-HSOR II
EC Number: EC 220.127.116.11 (It's important to note that EC 18.104.22.168 does not distinguish between Type 1, Type 2, etc. It includes all subtypes.)
Estradiol 17beta-dehydrogenase Type 2 (17bHSD2) performs oxidation, not reduction, catalyzing the conversion of estradiol onto estrone in humans using NAD+ as a cofactor. Type 1 performs the opposite action reducing estrone into estradiol. This article is specific to Type 2.
17bHSD2 appears to be most active in the small intestines. In one study 17bHSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17bHSD2 mRNA was found to be most abundant in the small intestine. 17bHSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the study suggested that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.
17bHSD2 dehydrogenates estradiol at the 17beta-hydroxy position (along with cofactors NAD+ and NADP+) into estrone (along with NADH, NADPH, and H+).
In this example 17bHSD2 converts estradiol into estrone. It uses NAD+ as a cofactor and produces NADH and H+ as byproducts. Note that this enzyme can also perform the opposite action. It is bidirectional.
|NAD+||NADH + H+|
This enzyme also catalyzes the conversion of the alcohol 1'-hydroxyestragole (a metabolite of the allylbenzene methyl chavicol) to the phenyl vinyl ketone 1'-oxoestragole, a reaction not catalyzed by cytochrome P450 enzymes. This reaction requires NAD+ (Nicotinamide adenine dinucleotide) as a cofactor. It produces NADH and H+ as byproducts.
|NAD+||NADH + H+|
Inhibitors and Inducers
|Potent Inhibitors||Strength||Dosage||Verified in Humans|
|Quercetin (in tea, apples, onions)||50% inhibition||IC50 = 1.5 µM||?|
|Linoleic acid||58% inhibition||0.018 mM||?|
|Linolenic acid||34% inhibition||0.018 mM||?|
|Naringenin (in grapefruit)||50% inhibition||IC50 = 14.4 µM||?|
|Oleic acid||100% inhibition||0.018 mM||?|
|Inhibitors||Strength||Dosage||Verified in Humans|
|Inducers||Strength||Dosage||Verified in Humans|
|All-trans retinoic acid (tretinoin)||5-10 fold increase||10-6 M||?|
|9-Cis-retinoic acid (alitretinoin)||5-10 fold increase||10-6 M||?|
|Gallic acid||30% induction||?||?|
|Genistein (in Kudzu) ||19.5% induction||100 nM||?|
|Genistein (in Kudzu) ||77% induction||?||?|
|Palm oil carotenoids||"significant stimulation"||0.001 mM||?|