The tripeptide
hormone, TRH, is metabolized by three
enzymes, the most specific of which is
pyroglutamyl peptide hydrolase-II (also termed
thyroliberinase), a metalloenzyme present in serum and brain. Because
pyroglutamyl peptidase-II activity in rat serum is regulated by
thyroid hormone levels, we tested the hypothesis that this activity is similarly altered in humans. We studied serum
pyroglutamyl peptidase-II activity in 6 patients with
hyperthyroidism, 18 patients with
hypothyroidism, and 31 euthyroid, normal weight volunteers. Because TRH [or its metabolite
cyclo(His-Pro)] is believed to be an important
hormone regulating appetite and metabolism, we also evaluated
pyroglutamyl peptidase-II activity in 27 euthyroid patients with
obesity. Serum
pyroglutamyl peptidase-II activity was elevated in patients with
hypothyroidism (mean +/- SEM, 33.9 +/- 3.7 nmol/mL.h) compared to that in euthyroid, normal weight volunteers (24.5 +/- 2.8 nmol/mL.h; P < 0.05), but not that in patients with
hyperthyroidism (28.3 +/- 4.1 nmol/mL.h; P = NS). Euthyroid obese patients had the highest
pyroglutamyl peptidase-II activity (43.6 +/- 2.8 nmol/mL.h; P < 0.0001 vs. normal weight volunteers).
Pyroglutamyl peptidase-II activity was positively correlated with body mass index (r2 = 0.30; P < 0.0001). After correction for body mass index, there were no difference in
pyroglutamyl peptidase-II activity in hypothyroid,
hyperthyroid, and euthyroid individuals. We conclude that serum
pyroglutamyl peptidase-II activity is regulated by, or regulates,
body weight.