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Subunit Gene Expression by Dopamine D2 Receptor Agonist in Clonal Mouse Gonadotroph
T3-1 Cells1
a Department of Obstetrics and Gynecology, Shimane Medical University, Izumo 693-8501, Japan
b Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
Pituitary prolactin biosynthesis is negatively regulated by hypothalamic dopamine through D2 receptors in pituitary lactotrophs, but little is known about the direct effect of dopamine on gonadotrophs. In this study, the clonal gonadotroph-derived cell line,
T3-1, was used to examine whether gene expression of the pituitary gonadotropin
subunit, stimulated with GnRH or pituitary adenylate cyclase-activating polypeptide (PACAP), was controlled by dopamine D2 receptor. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated the presence of dopamine D2 receptors in
T3-1 cells. Both GnRH and PACAP increased
subunit gene expression. GnRH-induced
subunit gene expression was not affected by quinpirol, a specific dopamine D2 receptor agonist. In contrast, PACAP-induced gene expression was significantly lower in the presence of quinpirol. The roles of extracellular signal-regulated kinase (ERK) and cAMP in the expression of the
subunit gene were examined. GnRH activated ERK, but PACAP did not, and the activation was not inhibited by quinpirol. GnRH-induced
subunit gene expression was completely inhibited by an ERK inhibitor, PD098059. Cyclic AMP accumulation in
T3-1 cells was increased by treatment with PACAP, and quinpirol inhibited this effect. GnRH did not affect cAMP production in these cells. These results suggest that in
T3-1 cells, dopamine D2 receptors negatively regulate pituitary
subunit gene expression in association with the cAMP-dependent pathway, but not with the ERK pathway.
2 Correspondence. FAX: 81-853-20-2264; kawa45{at}shimane-med.ac.jp
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