title: Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.
abstract: OBJECTIVE
  Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA.
  
  
  METHODS
  Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry.
  
  
  RESULTS
  DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis.
  
  
  CONCLUSIONS
  These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis.
authors.affiliation: Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Daniela B
authors.initials: DB
authors.lastname: Radl
authors.forename: Sandra
authors.initials: S
authors.lastname: Zárate
authors.forename: Gabriela
authors.initials: G
authors.lastname: Jaita
authors.forename: Jimena
authors.initials: J
authors.lastname: Ferraris
authors.forename: Verónica
authors.initials: V
authors.lastname: Zaldivar
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Eijo
authors.forename: Adriana
authors.initials: A
authors.lastname: Seilicovich
authors.forename: Daniel
authors.initials: D
authors.lastname: Pisera
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D052682:Lactotrophs / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism* / Q000502:physiology
chemical_list: D004967:Estrogens; D017448:Receptors, Dopamine D2; D004298:Dopamine