E2 17-beta-dehydrogenase 1, EC 1.1.1.62, 17-beta-hydroxysteroid dehydrogenase type 1, 17-beta-HSD 1, 20 alpha-hydroxysteroid dehydrogenase, 20-alpha-HSD, E2DH, Placental 17-beta-hydroxysteroid dehydrogenase, HSD17B1, E17KSR, EDH17B1, EDH17B2, EDHB17, HSD17, SDR28C1.
E2 17-beta-dehydrogenase 1, EC 1.1.1.62, 17-beta-hydroxysteroid dehydrogenase type 1, 17-beta-HSD 1, 20 alpha-hydroxysteroid dehydrogenase, 20-alpha-HSD, E2DH, Placental 17-beta-hydroxysteroid dehydrogenase, HSD17B1, E17KSR, EDH17B1, EDH17B2, EDHB17, HSD17, SDR28C1.
Hydroxysteroid (17-beta) Dehydrogenase 1 (HSD17B1) is an enzyme that plays a crucial role in the metabolism of steroid hormones. It is involved in the interconversion of estrogens and androgens, which are essential for various physiological processes. The human recombinant form of this enzyme is produced using recombinant DNA technology, allowing for its expression and purification in a controlled laboratory setting.
HSD17B1 is a member of the short-chain dehydrogenase/reductase (SDR) superfamily. It is a single, non-glycosylated polypeptide chain consisting of 352 amino acids and has a molecular mass of approximately 37.5 kDa . The enzyme catalyzes the reduction of estrone to estradiol and the oxidation of estradiol to estrone, using NADPH as a cofactor . This reaction is critical for regulating the biological activity of sex steroid hormones in various tissues, including the ovary, placenta, and mammary gland .
The human recombinant HSD17B1 is typically expressed in Escherichia coli (E. coli) using an expression vector such as pET28a . The expression is induced by adding isopropyl β-D-1-thiogalactopyranoside (IPTG) to the culture medium. The enzyme is then purified using Ni-NTA affinity chromatography, which exploits the His-tag fused to the N-terminus of the protein . This method allows for the efficient purification of large amounts of active enzyme, facilitating its functional study.
HSD17B1 plays a significant role in the regulation of estrogen exposure and estrogen-dependent growth of breast cancer tissue . By converting estrone, a weak estrogen, to estradiol, a potent estrogen, the enzyme influences the local concentration of active estrogens. This activity is crucial for the development and function of estrogen-responsive tissues. Additionally, HSD17B1 is involved in the biosynthesis of other steroid hormones, including androgens, progestins, glucocorticoids, and mineralocorticoids .
Given its role in estrogen metabolism, HSD17B1 is a potential target for therapeutic interventions in estrogen-dependent diseases such as breast cancer. Inhibitors of HSD17B1 could be used to block estradiol biosynthesis, thereby reducing estrogen exposure in target tissues . This approach may offer a new avenue for the treatment of hormone-dependent cancers and other conditions related to steroid hormone imbalance.