Imperial College London
Dr Olayiwola Oduwole

DrOlayiwolaOduwole

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2173o.oduwole

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Oduwole:2018:10.1172/JCI96794,
author = {Oduwole, OO and Peltoketo, H and Poliandri, A and Vengadabady, L and Chrusciel, M and Doroszko, M and Samanta, L and Owen, L and Keevil, B and Rahman, NA and Huhtaniemi, IT},
doi = {10.1172/JCI96794},
journal = {Journal of Clinical Investigation},
pages = {1787--1792},
title = {Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis},
url = {http://dx.doi.org/10.1172/JCI96794},
volume = {128},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor–null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr–/– mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.
AU  - Oduwole,OO
AU  - Peltoketo,H
AU  - Poliandri,A
AU  - Vengadabady,L
AU  - Chrusciel,M
AU  - Doroszko,M
AU  - Samanta,L
AU  - Owen,L
AU  - Keevil,B
AU  - Rahman,NA
AU  - Huhtaniemi,IT
DO  - 10.1172/JCI96794
EP  - 1792
PY  - 2018///
SN  - 0021-9738
SP  - 1787
TI  - Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI96794
UR  - http://hdl.handle.net/10044/1/58024
VL  - 128
ER  -
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