Search

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine known to control the proliferation and survival of stem cells including primordial germ cells and gonocytes. This led us to study the origin and regulation of testicular LIF. The LIF transcript was detected in the rat testis by RT-PCR from 13.5 days postcoitum until adulthood. LIF expression was investigated further in vitro in seven different highly purified testicular cell populations using 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 and postmeiotic germ cell-conditioned medium, and only low levels of LIF were detected in spermatogonia-conditioned medium. Large amounts of bioactive LIF were measured in testicular lymph. While LIF production was greatly enhanced in presence of serum, lipopolysaccharide, and TNFalpha further increased this production in peritubular and Sertoli cells, and human CG enhanced Leydig cell LIF production. In conclusion, peritubular cells are the principal source of testicular LIF, probably accounting for its high concentration in the lymph. Given the proliferative effect of LIF on immature germ cells, we suggest that peritubular LIF plays an important role in the regulation of testicular function.