Activation of D2 dopamine receptors inhibits estrogen response element-mediated estrogen receptor transactivation in rat pituitary lactotrophs

• Published in: Molecular and cellular endocrinology 2013-08, Vol.375 (1-2), p.58-67
• Main Authors: Ishida, Maho, Mitsui, Tetsuo, Izawa, Michi, Arita, Jun
• Format: Article
• Language: English
• Subjects: agonists; Animals; bromocriptine; Bromocriptine - pharmacology; Cells, Cultured; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; DNA; Dopamine; Dopamine Agonists - pharmacology; dopamine receptors; Estradiol - physiology; Estrogen; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; estrogen receptors; Estrogen response element; Female; gene expression; genes; Lactotroph; Lactotrophs - metabolism; messenger RNA; Pertussis Toxin - pharmacology; Phosphorylation; prolactin; Prolactin - genetics; Prolactin - metabolism; Protein Processing, Post-Translational; Rats; Rats, Wistar; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - metabolism; Response Elements; Second Messenger Systems; secretion; transcription (genetics); Transcriptional Activation
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2013.05.011

•Estrogen action was monitored using estrogen response element reporter assay.•D2 dopamine receptor stimulation inhibited the reporter activity in lactotrophs.•The inhibition was mediated in part by the PTX-sensitive G protein dependent pathway.•The inhibition was in part due to inhibition of cAMP/PKA pathway.•The similar inhibition was observed in somatomammotroph GH4ZR7 cell line. Estrogen and dopamine are major opposing regulators of the endocrine functions of pituitary lactotrophs. Dopamine inhibits estrogen-induced changes in the synthesis and secretion of prolactin, and lactotroph proliferation. We studied the mechanism of the inhibitory effects of dopaminergic stimulation on estrogen-induced functional changes of rat lactotrophs in primary culture. The dopaminergic agonist, bromocriptine (BC), suppressed 17β-estradiol-stimulated lactotroph proliferation, prolactin promoter activity, and mRNA expression of some estrogen-responsive genes. In lactotroph-enriched pituitary cells, BC treatment inhibited the estrogen response element (ERE) DNA sequence-mediated estrogen receptor (ER) transcriptional activity. Using a lactotroph-specific ERE transcriptional assay, we found that BC inhibition of the ERE-mediated ER transcriptional activity partly involved D2 dopamine receptor-mediated, pertussis toxin-sensitive G protein-coupled, cAMP/protein kinase A-dependent signaling. BC treatment had no effect on the cellular concentration of ERα or its phosphorylation status at Ser-118. Similar transcriptional inhibition by BC was also found in GH4ZR7 cells, a D2 dopamine receptor-expressing somatomammotrophic cell line. These results suggest that activation of the D2 dopamine receptors inhibits estrogen-dependent lactotroph functions in part via attenuation of ERE-mediated ER transactivation.