Use of Prolactin Receptor Antagonist to Better Understand Prolactin Regulation of Pituitary Homeostasis

Abstract

The anterior pituitary is permanently regulated by processes of apoptosis and proliferation in order to maintain tissue homeostasis. Several factors have been implicated in this regulation and lately, prolactin (PRL) has been included into that list. However, since PRL is secreted by anterior pituitary lactotropes, the actual outcome of its autocrine/paracrine actions on pituitary cells has remained difficult to assess. The availability of the pure PRL receptor antagonist Del1-9-G129R-hPRL has been helpful to circumvent this problem. While PRL has been traditionally associated with increased cell proliferation, recent studies revealed that this hormone actually induces apoptosis and decreases proliferation of anterior pituitary cells, by mechanisms involving the PRL receptor. The aim of this short review is to overview our current understanding of the regulation of pituitary homeostasis by PRL. Moreover, studies involving Del1-9-G129R-hPRL have helped anticipate to what extent future treatments involving PRL receptor inhibitors may interfere with processes regulated by PRL at the central level.

JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

“…The effect of PRL on a target tissue depends on the relative ratio of PRLR isoforms expressed [33]. So, we first used real-time PCR to evaluate the expression of PRLR long and PRLR short isoforms in the GH3 cell line and in the anterior pituitary gland from female rats.…”

“…The proapoptotic and antiproliferative effects of PRL on lactotropes are opposite to those exerted in the majority of PRL target tissues [2-8, 33]. Based on the evidence that the proapoptotic and antiproliferative actions of PRL are conserved in the somatolactotrope cell line GH3 [2], and that the PRLR isoform expression profile is similar to that observed in female rat anterior pituitary (Fig.…”

O efeito da prolactina na migração de células de câncer de mama pela remodelação da actina no citoesqueleto

“…Salienta-se que essas alterações das proteínas no citoesqueleto ocorreram após ativação do complexo PRL/PRLR que foi completamente bloqueado pelo emprego do RNA interferência (Ferraris et al, 2013). Além disso, outros investigadores sugerem que a resposta de sinalização intracelular que possa estar envolvida com a mobilização celular, possa ter a participação de vias oncogênicas, como a JAK2 e a STAT5 (Canbay et al, 1997;Xie et al, 2002), que podem estimular a proliferação de células cancerígenas e o crescimento tumoral (Goffin et al, 2005).…”

“…Em tumores periféricos, a inibição terapêutica do complexo PRL/PRLR e de sua via de sinalização oncogênica, pode ser feita utilizando antagonistas do PRLR, anticorpos bloqueadores e/ou RNA interferência (RNAi) que possuem potencial terapêutico e bloqueador da ação da PRL (Ferraris et al, 2013). Por essa razão, podemos empregar o RNAi em estudos experimentais para avaliar a via de sinalização da PRL.…”

Influência da temperatura de cultivo na expressão de proteínas recombinantes de interesse terapêutico no espaço periplásmico bacteriano, utilizando o promotor lambda PL

“…de rato, camundongo ou de origem humana. Utilizando abordagens farmacológicas para conseguir inibir a sinalização dos receptores de prolactina, estes estudos demonstraram que a retirada dos nove resíduos N-terminais do G129R-hPRL removeu o agonismo residual desta proteína e que a mesma compete eficazmente com a PRL na ligação com o receptor de prolactina (Ferraris, 2013).…”