title: Activation of D2 dopamine receptors inhibits estrogen response element-mediated estrogen receptor transactivation in rat pituitary lactotrophs.
abstract: 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.
authors.affiliation: Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan. mahoi@yamanashi.ac.jp
authors.forename: Maho
authors.initials: M
authors.lastname: Ishida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Mitsui
authors.forename: Michi
authors.initials: M
authors.lastname: Izawa
authors.forename: Jun
authors.initials: J
authors.lastname: Arita
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D052682:Lactotrophs / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D020218:Response Elements; D015290:Second Messenger Systems; D015533:Transcriptional Activation
chemical_list: D018491:Dopamine Agonists; D047628:Estrogen Receptor alpha; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases