Estradiol regulates the expression of c-FLIP in anterior pituitary cells

JAITA GABRIELA; ZÁRATE SANDRA; FERRARIS JIMENA; EIJO GUADALUPE; MAGRI LAURA; GOTTARDO MARÍA FLORENCIA; PISERA DANIEL; SEILICOVICH ADRIANA

Florencia

Congreso; ICE/ECE 2012; 2012

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, 17â-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.