Imperial College London
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DrBrynOwen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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bryn.owen05

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Owen:2016:10.1210/me.2015-1282,
author = {Owen, BM and Sondhi, V and Liu, J and Chomic, R and Kliewer, SA and Hughes, BA and Arlt, W and Mangelsdorf, DJ and Auchus, RJ},
doi = {10.1210/me.2015-1282},
journal = {Molecular Endocrinology},
pages = {469--478},
title = {Impaired 17,20-lyase activity in male mice lacking cytochrome b5 in Leydig cells},
url = {http://dx.doi.org/10.1210/me.2015-1282},
volume = {30},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5(flox/flox):Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings.
AU  - Owen,BM
AU  - Sondhi,V
AU  - Liu,J
AU  - Chomic,R
AU  - Kliewer,SA
AU  - Hughes,BA
AU  - Arlt,W
AU  - Mangelsdorf,DJ
AU  - Auchus,RJ
DO  - 10.1210/me.2015-1282
EP  - 478
PY  - 2016///
SN  - 1944-9917
SP  - 469
TI  - Impaired 17,20-lyase activity in male mice lacking cytochrome b5 in Leydig cells
T2  - Molecular Endocrinology
UR  - http://dx.doi.org/10.1210/me.2015-1282
UR  - http://hdl.handle.net/10044/1/30469
VL  - 30
ER  -
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