Cooperative effect of E2 and FGF2 on lactotroph proliferation triggered by signalling initiated at the plasma membrane

SOSA LILIANA DEL VALLE; GUTIÉRREZ SILVINA; PETITI JUAN PABLO; VACA, ALICIA MALDRE; DE PAUL ANA LUCÍA; TORRES ALICIA

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2013 vol. 305 p. 41 - 49

0193-1849

In the present work, we investigated the effect of 17beta-estradiol (E2) and basic fibroblast growth factor (FGF2) on the lactotroph cell proliferative response and the related membrane-initiated signalling pathway. Anterior pituitary mixed cell cultures of random cycling 3-month-old female rats were treated with 10nM of E2, E2 membrane-impermeable conjugated (E2-BSA), PPT (ERalfa agonist) and DPN (ERbeta agonist) alone or combined with FGF2 (10ng/ml) for 30min or 4h. Although our results showed that the uptake of BrdU into the nucleus of lactotrophs was not modified by E2 or FGF2 alone, a significant increase in the lactotrophs uptake of BrdU was observed after E2/FGF2 co-incubation, with this effect being mimicked by PPT/FGF2. These proliferative effects were blocked by ICI182780 or PD98059. The involvement of membrane ER in the proliferative response of prolactin cells induced by the steroid and FGF2 co-incubation was confirmed using E2-BSA, and the association between ERalpha and FGF receptor was observed after E2/FGF2 treatment by immunoprecipitation. A significant increase in the ERK1/2 expression was noted after E2, E2-BSA, PPT, and FGF2 alone, which was more noticeable after E2-BSA/FGF2, E2/FGF2, or PPT/FGF2 treatments. This study provides evidence that E2 and FGF2 exert a cooperative effect on the lactotroph proliferation principally by signaling initiated at the plasma membrane triggering a genomic effect mediated by MEK/ERK1/2, a common signaling pathway, that finally regulates the lactotroph population, thus contributing to pituitary plasticity.