Active and Total Transforming Growth Factor-{beta}1 Are Differentially Regulated by Dopamine and Estradiol in the Pituitary

RECOUVREUX MV; GUIDA MC; RIFKIN DB; BECU-VILLALOBOS D; DÍAZ TORGA G

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2011 vol. 152 p. 2722 - 2730

0013-7227

Dopamine, acting through the dopamine type2 receptor (Drd2), is the main inhibitor of pituitary prolactin secretion and lactotroph proliferation. TGF-b1 is involved, at least in part, in mediating these actions. It was described that TGF-b1 synthesis in rat pituitary lactotrophs is up-regulated by dopamine and down-regulated by estradiol. TGF-b1 is secreted as a large latent complex. The local regulation of cytokine activation in the pituitary has not yet been explored. In this work we studied pituitary active and total TGF-b1 content, as well as TGF-b1 mRNA, and the in vivo role of dopamine and estradiol on pituitary TGF-b1 levels. Adult female mice (wild-type), and female mice with a null mutation in the Drd2 (Drd2-/-) were used. The loss of dopaminergic tone induced a decrease in TGF-b1 mRNA expression, in active and total cytokine content, and in TGF-b type II receptor (TbRII) expression. Dopamine regulation of pituitary TGF-b1 activation process was inferred by the inhibition of active cytokine by in vivo sulpiride treatment.  Interestingly, in the absence of dopaminergic tone estradiol induced a strong increase in active TGF-b1. Prolactin (PRL) secretion correlated with active, but not total cytokine. TGF-b1 inhibitory action on lactotroph proliferation and PRL secretion was decreased in Drd2-/- pituitary cells, in correlation with decreased TbRII. The study of the TGF-b1 activation process and its regulation is essential to understand the cytokine activity. As an intermediary of dopamine inhibition of lactotroph function, TGF-b1 and local activators may be important targets in the treatment of dopamine agonist-resistant prolactinomas.