Anterior pituitary pyroglutamyl peptidase II activity controls TRH-induced prolactin release

Raymundo Cruz, Miguel Angel Vargas, Rosa Maria Uribe, Isel Pascual, Ivan Lazcano, Athanasios Yiotakis, Magdalini Matziari, Patricia Joseph-Bravo, Jean Louis Charli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Ecto-peptidases modulate the action of peptides in the extracellular space. The relationship between peptide receptor and ecto-peptidase localization, and the physiological role of peptidases is poorly understood. Current evidence suggests that pyroglutamyl peptidase II (PPII) inactivates neuronally released thyrotropin-releasing hormone (TRH). The impact of PPII localization in the anterior pituitary on the endocrine activities of TRH is unknown. We have studied whether PPII influences TRH signaling in anterior pituitary cells in primary culture. In situ hybridization (ISH) experiments showed that PPII mRNA was expressed only in 5-6% of cells. ISH for PPII mRNA combined with immunocytochemistry for prolactin, β-thyrotropin, or growth hormone, showed that 66% of PPII mRNA expressing cells are lactotrophs, 34% somatotrophs while none are thyrotrophs. PPII activity was reduced using a specific phosphorothioate antisense oligodeoxynucleotide or inhibitors. Compared with mock or scrambled oligodeoxynucleotide-treated controls, knock-down of PPII expression by antisense targeting increased TRH-induced release of prolactin, but not of thyrotropin. Similar data were obtained with either a transition-state or a tight binding inhibitor. These results demonstrate that PPII expression in lactotrophs coincides with its ability to control prolactin release. It may play a specialized role in TRH signaling in the anterior pituitary. Anterior pituitary ecto-peptidases may fulfill unique functions associated with their restricted cell-specific expression.

Original languageEnglish
Pages (from-to)1953-1964
Number of pages12
Issue number11
Publication statusPublished - Nov 2008
Externally publishedYes


  • Anterior pituitary
  • Growth hormone
  • Prolactin
  • Pyroglutamyl peptidase
  • TRH
  • Thyrotropin

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