Current knowledge of the multifunctional 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1).
At the late 1940s, 17β-HSD1 was discovered as the first member of the 17β-HSD family with its gene cloned. The three-dimensional structure of human 17β-HSD1 is the first example of any human steroid converting enzyme. The human enzyme's structure and biological function have thus been studied extensively in the last two decades. In humans, the enzyme is expressed in placenta, ovary, endometrium and breast. The high activity of estrogen activation provides the basis of 17β-HSD1's implication in estrogen-dependent diseases, such as breast cancer, endometriosis and non-small cell lung carcinomas. Its dual function in estrogen activation and androgen inactivation has been revealed in molecular and breast cancer cell levels, significantly stimulating the proliferation of such cells. The enzyme's overexpression in breast cancer was demonstrated by clinical samples. Inhibition of human 17β-HSD1 led to xenograft tumor shrinkage. Unfortunately, through decades of studies, there is still no drug using the enzyme's inhibitors available. This is due to the difficulty to get rid of the estrogenic activity of its inhibitors, which are mostly estrogen analogues. New non-steroid inhibitors for the enzyme provide new hope for non-estrogenic inhibitors of the enzyme.
Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China.
Wanhong
W
He
Amity Institute of Biotechnology, Amity University, Noida, UP, India.
Misra
M
Gauri
Laboratory of Endocrinology and Oncology, CHU de Québec Research Center and Laval University, Canada.
Tang
T
Li
Laboratory of Endocrinology and Oncology, CHU de Québec Research Center and Laval University, Canada.
Ruixuan
R
Wang
Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China; Laboratory of Endocrinology and Oncology, CHU de Québec Research Center and Laval University, Canada.
Sheng-Xiang
SX
Lin
D000728:Androgens / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D009928:Organ Specificity
D000728:Androgens; D004967:Estrogens; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human
17β-hydroxysteroid dehydrogenase (17β-HSD); Breast cancer; Dual sex-hormone modulation; Estrogen dependent disease; High activity in estrogen synthesis; Narrow binding tunnel