HSD17B1

This enzyme is responsible for the interconversion of estrone (E1) and estradiol (E2) and for the interconversion of androstenedione and testosterone:

17β-estradiol + NADP⁺ + ${\displaystyle \rightleftharpoons }$ estrone + NADPH + H⁺

testosterone + NADP⁺ + ${\displaystyle \rightleftharpoons }$ androstenedione + NADPH + H⁺

The human 17β-HSD1 isozyme is highly specific for estrogens over androgens whereas the rodent isozyme is less specific.[8]

Human 17β-HSD1 was the first enzyme of the 17β-HSD family to be cloned and to have its sequence identified.[9][10] Its three-dimensional structure is also the first example of any human steroid-converting enzyme.[11]

This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (αβα) sandwich known as a Rossmann fold. The human enzyme contains 327 amino acids and exists as a homodimer with two identical subunits of 34.5 kDa [10][12] The N-terminal short-chain dehydrogenase domain contains binding site for the NADP⁺/NADPH cofactor. A narrow, hydrophobic C-terminal domain contains a binding pocket for the steroid substrate.

Estradiol stimulates while dihydrotestosterone (DHT) inhibits breast cancer growth. Furthermore 17β-HSD1 levels positively correlate with estradiol and negatively correlate with DHT levels in breast cancer cells. Hence 17β-HSD1 represents a possible drug target for breast cancer treatment.[13]

• 17β-Hydroxysteroid dehydrogenase