title: Cooperative effect of E₂ and FGF2 on lactotroph proliferation triggered by signaling initiated at the plasma membrane.
abstract: In the present work, we investigated the effect of 17β-estradiol (E₂) and basic fibroblast growth factor 2 (FGF2) on the lactotroph cell-proliferative response and the related membrane-initiated signaling pathway. Anterior pituitary mixed-cell cultures of random, cycling 3-mo-old female rats were treated with 10 nM E₂, E₂ membrane-impermeable conjugated BSA (E₂-BSA), PPT (ERα agonist), and DPN (ERβ agonist) alone or combined with FGF2 (10 ng/ml) for 30 min or 4 h. 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 lactotroph uptake of BrdU was observed after E₂/FGF2 coincubation, with this effect being mimicked by PPT/FGF2. These proliferative effects were blocked by ICI 182,780 or PD-98059. The involvement of membrane ER in the proliferative response of prolactin cells induced by the steroid and FGF2 coincubation was confirmed using E₂-BSA, and the association between ERα 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.
authors: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Liliana del V
authors: Ldel V
authors: Sosa
authors: Silvina
authors: S
authors: Gutiérrez
authors: Juan P
authors: JP
authors: Petiti
authors: Alicia M
authors: AM
authors: Vaca
authors: Ana L
authors: AL
authors: De Paul
authors: Alicia I
authors: AI
authors: Torres
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D052682:Lactotrophs / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047628:Estrogen Receptor alpha; D016222:Fibroblast Growth Factor 2; D004958:Estradiol
keywords: 17β-estradiol; fibroblast growth factor 2; lactotroph proliferation; membrane estrogen receptor; mitogen-activated kinase effector kinase/extracellular signal-regulated kinase 1/2.