Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-β1, and TGF-β Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes

The neurotransmitter dopamine is known to inhibit prolactin secretion and the proliferation of lactotropes in the pituitary gland. In this study, we determined whether dopamine and TGFβ1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFβ1 secretion and TGFβ1 mRNA expression but inhibited lactotropic cell proliferation both in vivo and in vitro. The dopamine’s inhibitory action on lactotropic cell proliferation was blocked by a TGFβ1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFβ1 type II receptor and TGFβ1 mRNA levels and had undetectable levels of TGFβ1 protein. These cells showed a reduced TGFβ1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFβ1 and TGFβ1 type II receptor gene expression and recovered dopamine- and TGFβ1-induced growth inhibition in PR1 cells. The constitutive expression of D2 receptor short isoform also reduced the tumor cell growth rate. These data suggest that a TGFβ1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.