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Endocrinology, doi:10.1210/en.2005-0430
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Endocrinology Vol. 146, No. 10 4179-4188
Copyright © 2005 by The Endocrine Society

Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-ß1, and TGF-ß Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes

D. K. Sarkar, K. Chaturvedi, S. Oomizu, N. I. Boyadjieva and C. P. Chen

Endocrinology Program, Biomedical Division of the Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901

Address all correspondence and requests for reprints to: D. K. Sarkar, Endocrinology Program, Biomedical Division of the Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, New Jersey 08901. E-mail: sarkar{at}aesop.rutgers.edu.

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 TGFß1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFß1 secretion and TGFß1 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 TGFß1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFß1 type II receptor and TGFß1 mRNA levels and had undetectable levels of TGFß1 protein. These cells showed a reduced TGFß1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFß1 and TGFß1 type II receptor gene expression and recovered dopamine- and TGFß1-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 TGFß1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.




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