Gender differences in pituitary Kallikrein-Kinin system in normal and tumoral pituitaries.

FARAONI, ERIKA YANIL; ABELEDO-MACHADO, ALEJANDRA; DÍAZ -TORGA GRACIELA; CAMILLETTI, MARÍA ANDREA

Mar del PLata

Congreso; Sociedad Argentina de Investigación Clínica; 2018

SAIC

TGFβ1 is a known inhibitor of lactotroph function which biological activity is reduced in prolactinomas. We previously demonstrated that a pharmacological recovery of the local cytokine activity counteracts tumor development and decreases the hyperprolactinemia, representing an interesting tool for new treatments. Tissue Kallikrein (KLK1) was described as an important activator of latent TGFβ1. The Kallikrein-Kinin System (KKS) is complex; kininogens are cleaved by KLK1, releasing kinins: bradikinin and kallidin. Kinins exert their effect throw its receptors: B1 (B1R) and B2 (B2R), and are rapidly degraded by kininases I and II. Whereas B2R is constitutively expressed, B1R is inducible in pathological conditions and has a higher affinity for kinin metabolites. The aim of this work was to characterize pituitary KKS in normal pituitaries and prolactinomas. To this end, 8 month-old female and male mice lacking the dopamine receptor type 2 (Drd2KO) and WT counterparts were used. Only KO female develops pituitary hyperplasia and hyperprolactinemia. Pituitary expression of KKS was evaluated by RTqPCR. Statistical analysis: two-way ANOVA, followed by Tukey test. We found interesting gender differences: pituitary mRNA expression of most components of KKS was found significantly increased in males compared to females (KLK1, B2R, B1R, KininaseII). Regarding genotype differences, only KO females presented decreased pituitary expression of Klk1, with increased levels of Klkbp (KLK1 local inhibitor) and B1R compared to WT. In addition, the expression of KininaseII and B2R was found decreased in both male and female KO mice. Taken together, our results show a higher expression of pituitary KKS in males that correlates with higher levels of TGFβ1 and absence of prolactinoma development. We hypothesize that the weakened KKS found in KO-female pituitaries could be involved in prolactinoma development. Nevertheless, more in-depth studies are necessary to fully elucidate the role of KKS in the pituitary gland.