Activinas y desarrollo de prolactinoma parte II. Efectos de una ovariectomia

ALEJANDRA ABELEDO; RULLI SUSANA; FARAONI ERIKA YANIL; CAMILLETTI MARÍA ANDREA; AGUSTINA MARCIAL; GRACIELA DIAZ DE TORGA

Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

It was previously shown that a peripuberal ovariectomy (OVX) prevents pituitary hyperplasia in Drd2-/- and hCGβ+ female mice, indicating the participation of ovary factors in the development of prolactinoma. However, a hormonal replacement with estradiol after ovariectomy does not restore tumor development. These results suggest the participation of other ovarian factors. In this work, we propose that gonadal inhibins are involved in the development of these pituitary tumors. Inhibins and activins are members of the TGFβ family of proteins. Activins are homodimers composed of βA subunits (activin A) or βB subunits (activin B). Inhibins are heterodimeric proteins composed of an α subunit and one of two β subunits (βA or βB), giving rise to inhibin A (α?βA) or inhibin B (α?βB). Gonadal secreted inhibins antagonize, in the pituitary, the activin inhibitory function on lactotroph population. We postulate that a peripuberal OVX, induces alterations in the pituitary activin-inhibin system (Ac-In), preventing prolactinoma development. Pituitaries from adult Drd2-/- and hCGβ+ female mice, which develop prolactinoma, show a reduced mRNA expression (analyzed by qRT-PCR) of the Ac-In system components (βA and βB subunits, ActRI and ActRII receptors) when compared with wt counterpart. On the contrary, when Drd2-/- and hCGβ+ female mice are OVX at 2-month-old, they do not develop prolactinoma in the adulthood, and the pituitary expression of Ac-In system remains similar to those expressed by wt counterpart. According to these results we postulate that, after OVX, the decline in circulating inhibins restores pituitary activin inhibitory function on lactotroph population, preventing the development of prolactinoma.