Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.
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.
Radl
Daniela B
DB
Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Zárate
Sandra
S
Jaita
Gabriela
G
Ferraris
Jimena
J
Zaldivar
Verónica
V
Eijo
Guadalupe
G
Seilicovich
Adriana
A
Pisera
Daniel
D
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
D004967:Estrogens; D017448:Receptors, Dopamine D2; D004298:Dopamine