Endocrine Abstracts

Our previous results demonstrate that estrogens increase the expression of death receptors TNFRI and Fas in the anterior pituitary and sensitize anterior pituitary cells to pro-apoptotic factors. c-FLIP is a protein that interacts with procaspases 8 and 10 modulating death receptor activity. In normal tissues, two isoforms of c-FLIP have been identified, the short isoform (c-FLIPs) and the long one (c-FLIPL). c-FLIPs has an anti-apoptotic action whereas c-FLIPL has either anti-apoptotic, pro-apoptotic or proliferative actions depending on the tissue and its level of expression. To investigate whether c-FLIP is involved in the apoptosis of anterior pituitary cells, we evaluated the action of estradiol on c-FLIP expression in anterior pituitary cells from ovariectomized (OVX) Wistar rats and in the somatolactotrope cell line GH3. Both c-FLIPL and c-FLIPs, identified by Western blot, were detected in the anterior pituitary gland and GH3 cells. In cultured anterior pituitary cell from OVX rats, 17β-estradiol (E₂, 10-9M) increased the expression of c-FLIPL (control: 1.50±0.42, E₂: 1.91±0.59, P<0.05, t-test) but did not modify the expression of c-FLIPs (control: 0.30±0.05; E₂: 0.37±0.08). Also, the administration of E₂ (ip, 20 mg/100 g body weight) to OVX female rats increased the expression of c-FLIPL in the anterior pituitary (OVX: 5.7±0.40, OVX+E₂: 6.8±0.41, P<0.05, t-test) but did not modify the expression of c-FLIPs (OVX: 1.08±0.10; OVX+E₂: 1.18±0.05). The effect of E₂ on c-FLIPL expression was not observed in GH3 cells (control: 1.1±0.29; E₂: 0.9±0.13)

These results indicate that estrogens regulate the long isoform expression of cFLIP in the anterior pituitary suggesting that this action could be involved in the pro-apoptotic effect of estrogens in this gland.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.