Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Abstract

The distribution of the mRNA of the specific thyrotropin-releasing-hormone (TRH)-degrading enzyme pyroglutamyl peptidase II (EC 3.4.19.6) in rat tissues and brain regions and its regulation in rat tissues and in GH3 cells was studied by a reliable and quantitative solution hybridization ribonuclease protection assay. The distribution of pyroglutamyl peptidase II mRNA levels was uneven with the highest level of mRNA found in brain. Within brain the distribution of pyroglutamyl peptidase II mRNA was heterogeneous. A single dose of T₃ markedly increased the level of pyroglutamyl peptidase II mRNA in the pituitary (p < 0.01) and in the liver (p < 0.05). In GH3 cells, exposure to T₃ at concentrations from 10^–10 to 10^–6M for time periods of 2–24 h, did not change pyroglutamyl peptidase II mRNA levels. Acute administration of TRH to rats had no effect on pyroglutamyl peptidase II mRNA levels. By contrast, TRH down-regulated pyroglutamyl peptidase II mRNA in GH3 cells. A similar effect was produced in GH3 cells by activators of protein kinase C. These studies reveal fundamental differences in the mechanism of regulation of pyroglutamyl peptidase II mRNA in pituitary and in GH3 cells. Elevation of pyroglutamyl peptidase II mRNA in liver by T₃ suggests that this organ is the source of the enzyme in serum.

The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?

“…Trhde transcript levels and activity vary widely among brain regions, with highest values detected in cerebral cortex and hippocampus, as well as in cerebellar hemispheres, regions with limited Trh expression (Vargas et al, 1987;Vargas et al, 1992a;Heuer et al, 1998b;Lin and Wilk, 1998). In the adult rat brain, the map of Trhde transcript distribution is generally consistent with the proposal that it is expressed by neurons (Heuer et al, 1998b).…”

“…Trhde expression is at least 10fold higher in brain than in nine other organs of male or female Fisher 344 rats and this ratio is stable from 2 to 104 weeks (Yu et al, 2014) (Figure 2). Thus, the brain is the region with the highest TRH-DE specific activity in adult animals (Vargas et al, 1992a;Lin and Wilk, 1998).…”