Imperial College London
Alternate

Professor Kate Hardy

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Reproductive Biology
 
 
 
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Contact

 

+44 (0)20 7594 2106k.hardy

 
 
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Location

 

5-008Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Laird:2017:10.1210/en.2016-1538,
author = {Laird, M and Thomson, K and Fenwick, M and Mora, J and Franks, S and Hardy, K},
doi = {10.1210/en.2016-1538},
journal = {Endocrinology},
pages = {920--935},
title = {Androgen stimulates growth of mouse preantral follicles in vitro: interaction with follicle stimulating hormone and with growth factors of the TGFβ superfamily.},
url = {http://dx.doi.org/10.1210/en.2016-1538},
volume = {158},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aims of investigating interaction with FSH, the steroidogenic pathway and with growth factors of the TGFβ superfamily that are known to have a role in early follicle development.Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72h in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor (Fshr) expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was downregulated. The key androgen-induced changes in the TGFβ signaling pathway were downregulation of Amh, Bmp15 and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin, resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression.Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis and, importantly, implicate the intra-follicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.
AU  - Laird,M
AU  - Thomson,K
AU  - Fenwick,M
AU  - Mora,J
AU  - Franks,S
AU  - Hardy,K
DO  - 10.1210/en.2016-1538
EP  - 935
PY  - 2017///
SN  - 0013-7227
SP  - 920
TI  - Androgen stimulates growth of mouse preantral follicles in vitro: interaction with follicle stimulating hormone and with growth factors of the TGFβ superfamily.
T2  - Endocrinology
UR  - http://dx.doi.org/10.1210/en.2016-1538
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28324051
UR  - http://hdl.handle.net/10044/1/45264
VL  - 158
ER  -
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