JAK2/STAT5 pathway mediates prolactin-induced apoptosis of lactotropes

DE DIOS, NATALY; ORRILLO, SANTIAGO JORDI; IRIZARRI, MARTIN; THEAS, M; BOUTILLON, FLORENCE; CANDOLFI, MARIANELA; SEILICOVICH, ADRIANA; GOFFIN, VINCENT; PISERA, DANIEL; FERRARIS, JIMENA

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2019 vol. 108 p. 84 - 97

0028-3835

Prolactinomas are increasingly viewed as a ?problem of signal transduction?. So, the identification of factors and signalling pathways that control lactotrope cell turnover is needed in order to nourish new therapeutic developments. We have previously shown that prolactin (PRL) acts as a proapoptotic and antiproliferative factor on lactotropes, maintaining anterior pituitary cell homeostasis, which contrasts with the classical antiapoptotic and/or proliferative actions exerted by PRL in most of other target tissues. We aimed to investigate the PRLR-triggered signalling pathways mediating these non-classical effects of PRL in the pituitary. Globally, our results suggest that i) the PRLR/Jak2/STAT5 pathway is constitutively active in GH3 cells and contributes to PRL-induced apoptosis by increasing Bax/Bcl-2 ratio, ii) PRL inhibits ERK1/2 and Akt phosphorylation thereby contributing to its proapoptotic effect, and iii) PI3K/Akt participate in PRL-mediated control of lactotrope proliferation. We hypothesize that the alteration of PRL actions on in lactotrope homeostasis due to the dysregulation of any of the mechanisms of actions described above may contribute to the pathogenesis of prolactinomas.