Apoptosis related gene products in differentiated and tumorigenic rat Leydig cells and following regression induced by the cytotoxin ethane dimethanesulphonate
I. Woolveridge et al., Apoptosis related gene products in differentiated and tumorigenic rat Leydig cells and following regression induced by the cytotoxin ethane dimethanesulphonate, INT J ANDR, 24(1), 2001, pp. 56-64
Androgen secreting Leydig cells in the adult are differentiated with a very
low turnover, however, Leydig cell tumours can arise spontaneously or afte
r treatment with toxins. This study in the rat investigated whether changes
in components of programmed cell death could be involved. In contrast to t
heir absence in differentiated Leydig cells, antiapoptotic Bcl-2 and proapo
ptotic Bax were expressed in tumours. Bak and Bcl-xl were found in both tum
our and normal Levdig cells, Apoptosis was induced in subcutaneous implants
of Leydig cell tumour by ethane dimethanesulphonate (EDS) which is known t
o kill differentiated Leydig cells. The marked regression of the tumour fol
lowing EDS treatment was transient and re-growth occurred between 6 and 14
days later. Tumour regression and growth was associated with a similar weig
ht pattern in the seminal vesicles caused by changes in serum testosterone.
During tumour regression, clusterin and Bax proteins were elevated but Bak
, Bcl-xl and Bcl-2 were unchanged, Fas-R, Fas-L and Bax were upregulated af
ter tumour regression had taken place. These data show that Leydig cell tum
ours possess many of the apoptosis related gene products and carl die by ap
optosis, however, regulation is clearly different in differentiated and mit
otic Leydig cells.