Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice.
A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Jenna T
JT
Haverfield
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Peter G
PG
Stanton
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Kate L
KL
Loveland
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Heba
H
Zahid
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Peter K
PK
Nicholls
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Justine S
JS
Olcorn
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Yogeshwar
Y
Makanji
Priority Research Centres for Reproductive Science and Chemical Biology, School of Environmental and Life Sciences, Faculty of Science and Information Technology, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.
Catherine M
CM
Itman
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Evan R
ER
Simpson
Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
Sarah J
SJ
Meachem
D028341:Activins / Q000097:blood; D000818:Animals; D005640:Follicle Stimulating Hormone / Q000097:blood; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012707:Sertoli Cell Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013737:Testis / Q000378:metabolism / Q000473:pathology
C422405:activin A; C044147:activin B; C094377:inhibin-alpha subunit; D028341:Activins; D007265:Inhibins; D005640:Follicle Stimulating Hormone