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Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent

Daniela B Radl1, Sandra Zárate, Gabriela Jaita

  • 1Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Neuroendocrinology
|February 9, 2008
PubMed
Abstract

Insights

Dopamine (DA) induces apoptosis in anterior pituitary cells, specifically lactotrophs, but only when estrogen is present. This action is mediated by D2 receptors, suggesting DA controls lactotroph numbers via cell death.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Cell Biology

Background:

  • Dopamine (DA) regulates prolactin release and lactotroph proliferation via D2 receptors.
  • DA and 6-hydroxydopamine (6-OHDA) can induce apoptosis in various cell types.
  • Estradiol sensitizes anterior pituitary cells to proapoptotic stimuli.

Purpose of the Study:

  • Investigate the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells.
  • Determine the involvement of the D2 receptor and DA transporter (DAT) in the proapoptotic effect of DA.

Main Methods:

  • Cultured anterior pituitary cells from ovariectomized rats were used.
  • Cell viability was assessed using MTS assay.
  • Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL assays; lactotrophs were identified by immunocytochemistry.

Main Results:

  • DA induced lactotroph apoptosis in an estrogen-dependent manner.
  • Estradiol was not required for 6-OHDA-induced apoptosis.
  • D2 receptor activation (cabergoline) induced apoptosis, while antagonism (sulpiride) blocked DA-induced apoptosis.
  • DAT blockade (GBR12909) did not affect DA-induced apoptosis but inhibited 6-OHDA-induced apoptosis.

Conclusions:

  • DA induces apoptosis in estrogen-sensitized anterior pituitary cells via D2 receptor activation.
  • DA contributes to the regulation of lactotroph cell number by inducing apoptosis, in addition to inhibiting proliferation.

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