2 research outputs found
Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans
TRH-like peptides have been identified that differ from TRH
(pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like
immunoreactivity (TRH-LI) in human serum and urine by RIA with
TRH-specific antiserum 8880 or with antiserum 4319, which binds most
peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum
(< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27
normal subjects, 21 control patients, and 12 patients with carcinoid
tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because
serum was kept for at least 2 h at room temperature, which causes
degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is
not caused by these peptides. On high-performance liquid chromatography,
serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced
in, among others, the prostate. Urine of normals and control patients also
contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with
similar levels in males and females. TRH represented only 2% of urinary
TRH-LI, and anion-exchange chromatography and high-performance liquid
chromatography revealed that most TRH-LI in urine was < EEP-NH2. In
patients with carcinoid tumors, increased urinary TRH-LI levels were noted
(range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with
urinary creatinine, and the urinary clearance rate of TRH-LI was similar
to the glomerular filtration rate. In addition, serum TRH-LI was increased
in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum <
EEP-NH2 is cleared by glomerular filtration with little tubular
resorption. The possible role of the prostate as a source of urinary
TRH-LI was evaluated in 11 men with prostate cancer, showing a 25%
decrease in urinary TRH-LI excretion after prostatectomy (0.19 +/- 0.02
vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/- SEM). However, TRH-LI was
similar in spontaneously voided urine and in urine obtained through a
nephrostomy cannula from 16 patients with unilateral urinary tract
obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These
data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2,
which is cleared by renal excretion; 2) part of urinary < EEP-NH2 is
derived from prostatic secretion into the blood and not directly into
urine; and 3) urinary < EEP-NH2 can be used as marker for carcinoid
tumors
Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans
TRH-like peptides have been identified that differ from TRH
(pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like
immunoreactivity (TRH-LI) in human serum and urine by RIA with
TRH-specific antiserum 8880 or with antiserum 4319, which binds most
peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum
(< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27
normal subjects, 21 control patients, and 12 patients with carcinoid
tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because
serum was kept for at least 2 h at room temperature, which causes
degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is
not caused by these peptides. On high-performance liquid chromatography,
serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced
in, among others, the prostate. Urine of normals and control patients also
contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with
similar levels in males and females. TRH represented only 2% of urinary
TRH-LI, and anion-exchange chromatography and high-performance liquid
chromatography revealed that most TRH-LI in urine was < EEP-NH2. In
patients with carcinoid tumors, increased urinary TRH-LI levels were noted
(range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with
urinary creatinine, and the urinary clearance rate of TRH-LI was similar
to the glomerular filtration rate. In addition, serum TRH-LI was increased
in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum <
EEP-NH2 is cleared by glomerular filtration wit