IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Characterization of membrane progesterone receptors (mPRs) in the pituitary. Novel role of mPRα in the function of lactotroph population
Autor/es:
MARÍA ANDREA CAMILLETTI; MARÍA CECILIA BOTTINO; ALEJANDRA INÉS ABELEDO MACHADO; GRACIELA DÍAZ-TORGA; DANIEL PISERA; ERIKA YANIL FARAONI; JIMENA FERRARIS
Lugar:
Mar del Plata
Reunión:
Congreso; Sociedad Argentina de Investigación Clínica; 2016
Resumen:
Progesterone (P4) function on lactotroph population is controversial, being found proliferative and anti-proliferative effects. Our main objective is to study the involvement of P4 membrane receptors (mPRs) in lactotroph physiology and pathology. We first characterized the relative expression of P4 receptors (PRs) by qRT-PCR in pituitary glands of Sprague Dawley female rats in diestrus. Among all PRs, the PR-A represent the 62,4%, PR-B 23,3% and the mPRs represent the 14,3%. mPRα was the most abundant mPR isoform in the pituitary gland (40,8% of total mPRs). Then we conducted double immunofluorescence studies (mPRα; PRL) and flow cytometry analysis for characterization of this receptor in lactotroph population. We found that 54% of total pituitary cells are mPRα+. The 65% of lactotroph population is mPRα+. We next conducted a functional study with a mPR agonist: Org OD 02-0, Axon Medchem (OD). In an ex vivo experiment we incubated female mouse pituitaries in medium without (control) or with OD 100nM during 30 min. We measured the secreted PRL and the pituitary PRL content by RIA assay. We measured by specific ELISA, the pituitary content of active TGFβ1, potent inhibitor of lactotroph function. OD induced a strong increase in the pituitary levels of active TGFβ1. In accordance, OD induced a decrease in PRL secretion with concomitant increase in PRL content, reflecting the inhibition of PRL secretion. Finally, we measured the mPRα expression in two experimental models of prolactinoma: rats with chronic estradiol treatment and 8-month female mice with disruption of dopamine-type-2 receptor. In both models of prolactinoma the mPRα expression (q-RT-PCR) was found reduced compared with their respective controls. We postulate that the inhibitory effects of P4 on lactotrophs are mediated, at least in part, by mPRs, inducing TGFβ1 activation. mPRα expression was found decreased in experimental models of prolactinomas, a fact that could be involved in tumor development.