Impact of androstane A- and D-ring inversion on 17β-hydroxysteroid dehydrogenase type 3 inhibitory activity, androgenic effect and metabolic stability

2017 ◽  
Vol 25 (7) ◽  
pp. 2065-2073 ◽  
Author(s):  
Francisco Cortés-Benítez ◽  
Jenny Roy ◽  
René Maltais ◽  
Donald Poirier
Keyword(s):  
Inhibitory Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Metabolic Stability ◽  
Ring Inversion ◽  
Androgenic Effect ◽  
Type 3

scholarly journals A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

2015 ◽  
Vol 30 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Aisha Al-Sinani ◽  
Waad-Allah Mula-Abed ◽  
Manal Al-Kindi ◽  
Ghariba Al-Kusaibi ◽  
Hanan Al-Azkawi ◽  
...  
Keyword(s):  
Case Report ◽  
Novel Mutation ◽  
Hydroxysteroid Dehydrogenase ◽  
Review Of Literature ◽  
First Case ◽  
Type 3

scholarly journals Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171871 ◽  
Author(s):  
Lucie Carolle Kenmogne ◽  
Jenny Roy ◽  
René Maltais ◽  
Mélanie Rouleau ◽  
Bertrand Neveu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Tumor Models ◽  
Type 3

Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth

2016 ◽  
Vol 473 (8) ◽  
pp. 1037-1046 ◽  
Author(s):  
Bo Zhang ◽  
Xiao-Jian Hu ◽  
Xiao-Qiang Wang ◽  
Jean-François Thériault ◽  
Dao-Wei Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Crystal Structure ◽  
Cell Growth ◽  
Mcf7 Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Cancer Cell Growth ◽  
Down Regulation ◽  
Breast Cancer Cell Growth ◽  
Type 3 ◽  
First Time

Human 3α-HSD3 (3α-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5α-DHT (5α-dihydrotestosterone). The present study attempts to obtain the important structure of 3α-HSD3 in complex with 5α-DHT and to investigate the role of 3α-HSD3 in breast cancer cells. We report the crystal structure of human 3α-HSD3·NADP+·A-dione (5α-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5α-DHT in the presence of NADP+. Although 5α-DHT was introduced during the crystallization, oxidoreduction of 5α-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3α-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5α-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3α-HSD3·NADP+·4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3α-HSD3 expression without interfering with 3α-HSD4, which shares a highly homologous active site, the 5α-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5α-DHT reverse binding within 3α-HSD3, and demonstrates for the first time that down-regulation of 3α-HSD3 decreases MCF7 breast cancer cell growth.

17β-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up

2020 ◽  
Vol 43 (12) ◽  
pp. 1711-1716
Author(s):  
M. F. Faienza ◽  
F. Baldinotti ◽  
G. Marrocco ◽  
N. TyuTyusheva ◽  
D. Peroni ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Female Sex ◽  
Sex Assignment ◽  
Type 3

scholarly journals Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?

2013 ◽  
Vol 2013 (1) ◽  
Author(s):  
Janet Chuang ◽  
Amy Vallerie ◽  
Lesley Breech ◽  
Howard M Saal ◽  
Shumyle Alam ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Gender Assignment ◽  
Type 3
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