title: Anterior pituitary pyroglutamyl peptidase II activity controls TRH-induced prolactin release.
abstract: 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, beta-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.
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Av. Universidad 2001, Cuernavaca, Mor. 62271, Mexico.
authors.forename: Raymundo
authors.initials: R
authors.lastname: Cruz
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Vargas
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Uribe
authors.forename: Isel
authors.initials: I
authors.lastname: Pascual
authors.forename: Ivan
authors.initials: I
authors.lastname: Lazcano
authors.forename: Athanasios
authors.initials: A
authors.lastname: Yiotakis
authors.forename: Magdalini
authors.initials: M
authors.lastname: Matziari
authors.forename: Patricia
authors.initials: P
authors.lastname: Joseph-Bravo
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Charli
mesh_terms: D000626:Aminopeptidases / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D017403:In Situ Hybridization; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D011388:Prolactin / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D011761:Pyrrolidonecarboxylic Acid