CONICET | Buscador de Institutos y Recursos Humanos

Activins are members of the transforming growth factor beta (TGFβ) family of proteins. They are biologically active as dimers and, besides their known function on pituitary gonadotrophs, activins (A and B) 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, as 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, which develop prolactinoma, present a decrease in the expression of several components of Ac-In system: βA and βB subunits, ActRIB and ActRII activin receptors. Moreover, an increase in FST protein expression (activin antagonist) was observed in both mice models of prolactinoma when compared to wt female mice. On the other hand, male pituitaries from both mice models present higher expression of Ac-In components compared to females, without genotype differences. According to these results, we postulate that: as activins inhibit lactotroph function, a decrease in the 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+), and a higher expression of Ac-In system in male pituitaries, which present an absence of adenoma, could be protecting this sex from prolactinoma development.