Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta 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 TGFbeta1 interact to regulate lactotropic cell proliferation. We found that dopamine and the dopamine agonist bromocriptine stimulated TGFbeta1 secretion and TGFbeta1 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 TGFbeta1-neutralizing antibody. We also found that PR1 cells, which express low amounts of the dopamine D2 receptor, demonstrated reduced expression of TGFbeta1 type II receptor and TGFbeta1 mRNA levels and had undetectable levels of TGFbeta1 protein. These cells showed a reduced TGFbeta1 growth-inhibitory response. Constitutive expression of the D2 receptor short isoform, but not the D2 receptor long isoform, induced TGFbeta1 and TGFbeta1 type II receptor gene expression and recovered dopamine- and TGFbeta1-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 TGFbeta1 system may mediate, in part, the growth-inhibitory action of dopamine on lactotropes.
Sarkar
D K
DK
Endocrinology Program, Biomedical Division of the Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick 08901, USA. sarkar@aesop.rutgers.edu
Chaturvedi
K
K
Oomizu
S
S
Boyadjieva
N I
NI
Chen
C P
CP
D030201:Activin Receptors, Type I / Q000235:genetics / Q000502:physiology; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007028:Hypothalamic Hormones / Q000378:metabolism; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
D007028:Hypothalamic Hormones; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; C030304:lactotropin; D001971:Bromocriptine; D004958:Estradiol; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D004298:Dopamine