17ò-Hydroxysteroid dehydrogenase 1 (17ò-HSD1) is an enzyme that in humans is encoded by the HSD17B1 gene. This enzyme oxidizes or reduces the C17 hydroxy/keto group of androgens and estrogens and hence is able to regulate the potency of these sex steroids
This enzyme is responsible for the interconversion of estrone (E1) and estradiol (E2) and for the interconversion of androstenedione and testosterone:
The human 17ò-HSD1 isozyme is highly specific for estrogens over androgens whereas the rodent isozyme is less specific.
Human 17ò-HSD1 was the first enzyme of the 17ò-HSD family to be cloned and to have its sequence identified. Its three-dimensional structure is also the first example of any human steroid-converting enzyme.
This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (ñòñ) 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 The N-terminal short-chain dehydrogenase domain contains binding site for the NADP<sup>+</sup>/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 17ò-HSD1 levels positively correlate with estradiol and negatively correlate with DHT levels in breast cancer cells. Hence 17ò-HSD1 represents a possible drug target for breast cancer treatment.