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 TGF beta 1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGF beta 1 secretion and TGF beta 1 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 TGF beta 1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGF beta 1 type II receptor and TGF beta 1 mRNA levels and had undetectable levels of TGF beta 1 protein. These cells showed a reduced TGF beta 1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGF beta 1 and TGF beta 1 type II receptor gene expression and recovered dopamine- and TGF beta 1-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 TGF beta 1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.