Activins and prolactinoma development I. Gender differences

ABELEDO MACHADO, ALEJANDRA INÉS; DÍAZ -TORGA GRACIELA; FARAONI, ERIKA YANIL; CAMILLETTI, MARÍA ANDREA; MARCIAL-LOPEZ, C AGUSTINA; RULLI, SUSANA B

Mar del PLata

Congreso; Sociedad Argentina de Investigación Clínica; 2018

SAIC

Activins are members of the transforming growth factor beta (TGFβ) family of proteins. They are homodimers composed of βA subunits (activin A) or βB subunits (activin B). Besides their known function on pituitary gonadotrophs, activins also modulate lactotroph population, being inhibitors of cell proliferation and prolactin secretion. Its inhibitory function is modulated by inhibins and follistatin (FST). Up today, the role of activins in prolactinoma development remains unknown. We propose that alterations in the pituitary activin-inhibin system (Ac-In) are involved in prolactinoma development. In this work, we studied the pituitary expression (mRNA by RTqPCR) of Ac-In components in two experimental models of prolactinoma: mice deficient in dopamine receptor type 2 (Drd2 -/-) and mice over-expressing the β subunit of human chorionic gonadotropin (hCGβ+). These animal models present sex differences: an increase in the pituitary size and hyperprolactinemia are observed only in adult female transgenic mice, but not in males. We found that pituitaries from Drd2-/- and hCGβ+ females (prolactinomas) present decreased expression of several components of Ac-In system: βA and βB subunits, and activin receptors (ActRIB, ActRII), concomitant with an increase in FST expression (activin antagonist). On the other hand, male pituitaries (both mice models) present higher expression of Ac-In components compared to females, without genotype differences. According to these results, we postulate that: 1- As activins are inhibitors of lactotroph function, a decreased expression of Ac-In system (βA, βB, receptors), concomitant with an increase in FST expression, is involved in prolactinoma development in transgenic female mice (Drd2-/- and hCGβ+); 2- The higher expression of Ac-In system found in male pituitaries (absence of adenoma), could be protecting this sex from prolactinoma development.