Effect of estradiol on the expression of the TNF-alpha/ TNFR1 system in the anterior pituitary cells.

SEILICOVICH ADRIANA; ZALDIVAR VERÓNICA; MAGRI LAURA; ZÁRATE SANDRA; JAITA GABRIELA; EIJO GUADALUPE; PISERA DANIEL

Tokio,

Congreso; 14 International Congress of Endocrinology, Tokio, Japon; 2010

Tumor necrosis factor á (TNF-á) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-a-induced apoptosis of anterior pituitary (AP) cells from female rats (especially lactotropes) is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. In addition, we showed that estradiol not only potentiates the proapoptotic effect of TNF-a in somatotropes, but also has an apoptotic action per se in these cells. The aim of the present study was to evaluate the effect of estrogens on the expression of TNF-á and its receptor TNFR1 inAP cells. In cultured AP cells from ovariectomized rats (OVX), 17â-estradiol (E2, 10-9M) increased the expression of TNF-á mRNA (C: 1.00 ± 0.07, E2: 1.39 ± 0.06; p<0.01) but did not modify the expression of TNFR1 (RT-PCR). To study which of the AP cell subpopulations could be involved in these changes we determined by immunocytochemistry the effect of E2 on TNF-á and TNFR1 expression in AP cells. E2 significantly increased the percentage of total anterior pituitary cells (C: 22.0%, E2:26.6%, p<0.01, c2) and lactotropes (C:32.8%, E2:41.4%, p<0.01, c2) but not somatotropes (C:74.3%, E2:72.7%) expressing TNF-á. E2 also increased the percentage of TNFR1-positive AP cells (C: 13.2%, E2:19.7%, p<0.01, c2) and TNFR1–positive lactotropes (C:9.7%, E2:25.4%, p<0.01, c2). Taken together these results indicate that estrogens, by increasing the expression of the TNF-á/TNFR1 system could sensitize AP cells to apoptotic stimuli at proestrus.