17B-estradiol modulates the prolactin secretion induced by TRH through membrane estrogen receptors via PI3K/Akt in female rat anterior pituitary cell culture.

SOSA LILIANA DEL VALLE; GUTIÉRREZ SILVINA; PETITI JUAN PABLO; PALMERI CLAUDIA MARIELA; MASCANFRONI IVÁN; SOAJE MARTA; DE PAUL ANA LUCÍA; TORRES ALICIA INÉS

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

AMER PHYSIOLOGICAL SOC

Año: 2012 vol. 302 p. 1189 - 1197

0193-1849

Considering that estradiol is a major modulator of prolactin (PRL) secretion, the aim of the present study was to analyze the role of membrane ERα (mERα) in the regulatory effect of this hormone on the PRL secretion induced by TRH, by focusing on the PI3K/Akt pathway activation. Anterior pituitary cell cultures from female rats were treated with 17β-estradiol (E2, 10nM) and its membrane-impermeable conjugated estradiol (E2-BSA, 10nM) alone or co-incubated with TRH (10nM) for 30min, with PRL levels being determined by RIA. Although E2, E2-BSA, TRH and E2/TRH differentially increased the PRL secretion, the highest levels were achieved with E2-BSA/TRH. ICI 182,780 did not modify the TRH-induced PRL release, but significantly inhibited the PRL secretion promoted by E2 or E2-BSA alone or in co-incubation with TRH. The PI3K inhibitors LY294002 and wortmannin partially inhibited the PRL release induced by E2-BSA, TRH and E2/TRH, and totally inhibited the PRL levels stimulated by E2-BSA/TRH, suggesting that the mER mediated the cooperative effect of E2 on TRH-induced PRL release through the PI3K pathway. Also, the involvement of this kinase was supported by the translocation of its regulatory subunit p85α from the cytoplasm to the plasma membrane in the lactotroph cells treated with E2-BSA and TRH alone or in co-incubation. A significant increase of phosphorylated Akt was induced by E2-BSA/TRH. Finally, the changes of ERα expression in the plasmalemma of pituitary cells were examined by confocal microscopy and FACS analysis, which revealed that the mobilization of intracellular ERα to the plasma membrane of lactotroph cells was only induced by E2. These finding showed that E2 may act as a modulator of the secretory response of lactotrophs induced by TRH through mER, with the contribution by PI3K/Akt pathway activation providing a new insight into the mechanisms underlying the non-genomic action of E2 in the pituitary.