Leukemia inhibitory factor expression and regulation within the testis

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine known to control the proliferation and survival of stem cells including primordial germ cel ls and gonocytes. This led us to study the origin and regulation of testicu lar LIF. The LIF transcript was detected in the rat testis by RT-PCR from 1 3.5 days postcoitum until adulthood. LIF expression was investigated furthe r in vitro in seven different highly purified testicular cell populations u sing RT-PCR and bioassays combined with neutralization experiments. LIF was found to be produced by peritubular cells and, to a much lesser extent, by the other testicular somatic cell types. No LIF was detected in meiotic an d post-meiotic germ cell-conditioned medium, and only low levels of LIF wer e detected in spermatogonia-conditioned medium. Large amounts of bioactive LIF were measured in testicular lymph. While LIF production was greatly enh anced in presence of serum, lipopolysaccharide, and TNF alpha further incre ased this production in peritubular and Sertoli cells, and human CG enhance d Leydig cell LIF production. In conclusion, peritubular cells are the prin cipal source of testicular LIF, probably accounting for its high concentrat ion in the lymph. Given the proliferative effect of LIF on immature germ ce lls, we suggest that peritubular LIF plays an important role in the regulat ion of testicular function.