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In vitro regulation of rat Sertoli cell transferrin expression by tumor necrosis factor α and retinoic acid

1999; Elsevier BV; Volume: 148; Issue: 1-2 Linguagem: Inglês

10.1016/s0303-7207(98)00199-3

1872-8057

Francesco Sigillo, Florian Guillou, I. Fontaine, Mohamed Benahmed, Brigitte Le Magueresse‐Battistoni,

RNA Interference and Gene Delivery

In the present study, we examined the in vitro regulation of 20-day-old rat Sertoli cell transferrin expression by tumor necrosis factor α (TNFα), a paracrine factor produced by germ cells. Addition of TNFα to highly purified cultured Sertoli cells resulted in a dose and time-dependent enhancement in the levels of transferrin mRNA (Northern-blot) and protein (RadioImmunoAssay) with an ED50 of 120pM. Co-treatment of Sertoli cells with the optimal dose of retinoic acid (RA, a potent inducer of transferrin) and TNFα induced a stimulation of transferrin that was significantly higher than the FIRT combination, a well known mixture of transferrin activators. Actinomycin D inhibited the effects of TNFα and of RA, suggesting that ongoing RNA synthesis was required to enhance transferrinn. We next demonstrated that RA and TNFα exerted additive effects on transferrin expression as assessed by dose-response and kinetics studies. Moreover pre-treatment with RA, while greatly increasing the amount of transferrin produced, did not modify Sertoli cell responsiveness to TNFα. Together these results show that TNFα and RA are likely to act independently, additively and at least at the transcriptional level to increase transferrin expression.