Activins and prolactinoma development II. Effects of an ovarictomy.

FARAONI E, MARCIAL A, ABELEDO A, CAMILLETTI MA, RULLI S, DÍAZ-TORGA G

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC

It was previously shown that an ovariectomy (OVX) prevents pituitaryhyperplasia in Drd2-/- and hCGβ+ female mice, indicating theparticipation of ovarian factors in the development of prolactinoma.However, a hormone replacement with estradiol after OVX does notrestore tumor development. These results suggest the participationof other ovarian factors. In this work, we propose that gonadal inhibinsare 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 βBsubunits (activin B). Inhibins are heterodimeric proteins composedof a α subunit and a β subunit (βA or βB), giving rise to inhibin A (α?βA) or inhibin B (α?βB). Gonadal secreted inhibins antagonize, inthe pituitary, the activin inhibitory function on lactotroph population.We postulate that an OVX, induces alterations in the pituitary activin-inhibin system (Ac-In), preventing prolactinoma development.Results: Pituitaries from adult Drd2-/- and hCGβ+ female mice (prolactinomas)show a reduced mRNA expression (analyzed by RTqPCR)of the Ac-In system components (βA and βB subunits, ActRIand ActRII receptors) when compared with WT counterpart. On thecontrary, when Drd2-/- and hCGβ+ female mice are ovariectomizedat 2-month-old, they do not develop prolactinoma in the adulthood,and the pituitary expression of Ac-In system remains similar to thoseexpressed in WT counterpart. According to these results we postulatethat, after OVX, the decline in circulating inhibins restores thepituitary activin inhibitory-function on lactotroph population, preventingthe development of prolactinoma.