| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Hôpital Saint-Luc, et Départements de Médecine et Biochimie (R.L.), Université de Montréal, Montréal, Québec, Canada H2X 1P1
Address all correspondence and requests for reprints to: Pierre D’Amour, M.D., Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Hôpital Saint-Luc, 264 René Lévesque boulevard East, Montréal, Québec, Canada H2X 1P1. E-mail: rechcalcium{at}ssss.gouv.qc.ca
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In vivo experimentation in rats
Experimental protocol. Male Sprague Dawley rats, weighing
225–250 g, were fed a normal diet until experimentation. They were
kept in cages according to the guidelines of the Canadian Council on
Animal Care. The protocol was approved by the animal care committee of
our center for study of groups of six to eight rats. Under anesthesia
with isoflurane delivered in
N2O:O2 (4:1), TPTX was
performed in all except one group (sham-operated). Catheters were
installed in the right femoral vein for iv infusion and in the bladder
for urine collection. Solvent was infused at 50 µl/min over the first
2 h in all groups and continued for another 2 h in the
sham-operated control group and one TPTX group, while all other TPTX
groups were infused for 2 h with the following preparations:
hPTH-(1–84) or hPTH-(1–34), 1 nmol/h; hPTH-(1–84) or hPTH-(1–34), 1
nmol/h with hPTH-(7–84), 1, 3, or 10 nmol/h or hPTH-(39–84), 10
nmol/h or a mixture of synthetic C-fragments [10% hPTH-(7–84), 45%
each of hPTH-(39–84) and hPTH-(53–84)], 1 or 10 nmol/h. hPTH-(7–84)
and the C-fragment mixture (10 nmol/h) were also infused alone. Blood
was obtained from the tail vein to measure Ca2+
at 0, 1, 2, 3, and 4 h. The rats were killed by exsanguination
through the abdominal aorta at 4 h, and total calcium, phosphate,
and creatinine were also measured. Urine was collected during the last
hour of the 4-h experimentation period. All samples were aliquoted and
stored at -75 C until assayed.
Materials and methods. Ca2+ was analyzed on total blood using an ICA-2 analyzer (Radiometer, Copenhagen, Denmark). The interassay coefficients of variation for 38 determinations at concentrations of 0.77 and 1.75 mmol/liter were 3.3% and 2.7%, respectively. Serum total calcium, phosphate, and creatinine and urinary phosphate and creatinine were measured by an automated colorimetric method. Urinary calcium was quantitated by atomic absorption spectrometry.
Statistical analysis. The results are the mean ± SD. The data were analyzed using Student’s t test or one-way ANOVA, followed by Student- Newman-Keuls test for 2 by 2 comparisons. Serum and urinary parameter results were not available for all time points except at 4 h, when most group differences were analyzed.
Experimentation in vitro with ROS 17/2.8 clonal cells
Cell culture. Rat osteosarcoma cells, ROS 17/2.8, were
maintained in 75-cm2 flasks containing
DMEM-Ham’s F-12 medium supplemented with 28 mmol
NaHCO3 (pH 7.4), 1% penicillin-streptomycin
(Life Technologies, Inc., Grand Island, NY), and 10%
fetal serum (HyClone Laboratories, Inc., Logan, UT). They
were maintained in a humidified atmosphere of 95% air and 5%
CO2 for 5 days. Confluent cells were removed from
the culture flasks with 0.25% trypsin-1 mM EDTA
(Life Technologies, Inc.) and suspended in the same medium
supplemented with 100 nM dexamethasone (ICN Biomedical,
Costa Mesa, CA) to enhance the cAMP response to PTH (31).
They were then plated onto 12-well sterile plates at a density of
2 x 104 cells/cm2 and
grown in the same medium for 5 days, with a medium change on the third
day. The cells were finally used for cAMP stimulation as well as for
binding experiments. The mean cell density per well on day 5 was
235,000 ± 18,141 cells (mean ± SEM; n =
23).
PTH bioassay. One milliliter of [3H]adenine (Amersham Pharmacia Biotech, Oakville, Canada; 1 µCi/ml) in DMEM-Ham’s F-12 and 2% fetal serum was added to each well for 2 h at 37 C. The wells were then washed twice with 1 ml medium and incubated for 10 min with 250 µl medium containing 1 mM isobutylmethylxanthine (ICN Biomedicals, Inc., Irvine, CA) to prevent cAMP breakdown (31). PTH preparations were then added in 250 µl medium, and incubation was allowed to continue for 5 more min at room temperature. After washing each well twice with 1 ml 5% cold PBS, the reaction was stopped with 1 ml 5% trichloroacetic acid. Each well and plate were reincubated for a minimum of 2 h. [14C]cAMP (Amersham Pharmacia Biotech, Arlington Heights, IL; 2000 cpm) was then added to each well. Trichloroacetic acid extracts were eluted through Dowex (Bio-Rad Laboratories, Inc.) and alumina (Fisher Scientific, Nepean, Canada) columns to determine [3H]- and [14C]cAMP counts, as described by Salomon et al. (32) and modified by Meeker and Harden (33). Radioactivity was counted in 10 ml Scintisafe (Fisher Scientific) in a Beckman Coulter, Inc., S-1801 scintillation counter (Palo Alto, CA). Synthetic hPTH-(1–84), hPTH-(7–84), and hPTH-(1–34) were bioassayed at concentrations ranging from 5 x 10-7 to 10-11 M.
Binding studies. Synthetic [Nle8,
18,Tyr34]hPTH-(1–34) and
[Tyr34]hPTH-(19–84) were iodinated by the
chloramine-T method, using Na125I (Amersham Pharmacia Biotech), and were purified by HPLC. Each well was
rinsed twice with 1 ml binding buffer [50 mM Tris-HCl (pH
7.7), 100 mM NaCl, 5 mM KCl, 2 mM
CaCl2, 0.5% BSA, and 10% hypoparathyroid dog
serum] and then incubated for 4 h at 16 C with 2 x
105 cpm 125I-labeled tracer
with or without various molar concentrations of cold PTH preparations
in a final volume of 500 µl. The unbound radioligand was removed, and
the cell monolayers were rinsed twice with 1 ml cold PBS. The cells
were lysed with 500 µl 1 M NaOH, and the lysates were
counted in an LKB-1277 
-counter (Rockville, MD).
hPTH-(1–84), hPTH-(1–34), and hPTH-(7–84) concentrations were
similar to those described previously for the PTH bioassay.
Statistical analysis. Results are the mean ± SD. Results obtained with the various PTH preparations were analyzed by one-way ANOVA, followed by Student-Newman-Keuls test for 2 by 2 comparisons.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
summarizes the evolution of
serum parameters of calcium and phosphate homeostasis over 2 h
after TPTX in rats as well as the change in the same parameters in
sham-operated control rats. Ionized calcium
(Ca2+) decreased by 0.19 ± 0.03 mmol/liter
(P < 0.0001) and total calcium by 0.40 ± 0.17
mmol/liter (P < 0.0001), whereas serum phosphate
increased by 0.26 ± 0.40 mmol/liter (P < 0.0001)
in TPTX animals, all very significant differences. Serum creatinine
also decreased slightly, by 2.6 ± 5.7 µmol/liter
(P < 0.001), as an indication of volume expansion.
There was no change in these serum measurements in sham-operated
control rats over the same time period. Serum creatinine also tended to
decrease by 4.1 ± 7.3 µmol/L in these rats, but this did not
reach statistical significance in this smaller group.
|
summarizes calcemic responses
observed during 2-h infusion of various PTH preparations or solvent
alone in TPTX rats as well as the effect of infusion of solvent alone
in sham-operated control rats. In these animals, the
Ca2+ concentration remained normal and unchanged
during the 2-h infusion. In TPTX animals infused with solvent alone,
the Ca2+ concentration remained low at 1.10
mmol/liter and did not change over the time course of the experiment.
hPTH-(7–84) (10 nmol/h) caused a decrease in the
Ca2+ concentration of 0.18 ± 0.02
mmol/liter, whereas fragment mixture (10 nmol/h) reduced it by only
0.07 ± 0.04 mmol/liter over the same time period; both results
were significantly different (P < 0.001) from those in
TPTX solvent alone rats. hPTH-(1–84) (1 nmol/h) increased ionized
calcium by 0.16 ± 0.03 mmol/liter (P < 0.001).
When hPTH-(1–84) (1 nmol/h) was infused with hPTH-(7–84) (10 nmol/h),
Ca2+ did not increase and remained stable at the
concentration observed in TPTX animals infused with solvent alone.
Fragment mixture (10 nmol/h) did not inhibit and, in fact, slightly
enhanced the calcemic effect of hPTH-(1–84) (1 nmol/h). hPTH-(1–34)
(1 nmol/h) increased ionized calcium values by 0.19 ± 0.03
mmol/liter (P < 0.001) over 2 h. Rats infused
with hPTH-(7–84) (10 nmol/h) with hPTH-(1–34) (1 nmol/h) maintained a
lower Ca2+ concentration than TPTX animals
infused with solvent alone, but higher than values obtained with
hPTH-(7–84) (10 nmol/h) alone. hPTH-(7–84) (3 nmol/h) with
hPTH-(1–34) (1 nmol/h) resulted in Ca2+ values
higher than those found in TPTX animals infused with solvent alone, but
lower than those observed with hPTH-(1–34) (1 nmol/h) alone. The
fragment mixture (10 nmol/h) with hPTH-(1–34) (1 nmol/h) was slightly
more potent than hPTH-(7–84) (3 nmol/h) in limiting the calcemic
response to hPTH-(1–34).
|
summarizes differences in
Ca2+ and PO4 concentrations
obtained over 2-h infusion of the same PTH preparations. The
differences in Ca2+ concentration were similar to
those described above. hPTH-(7–84) alone (10 nmol/h) reduced the
phosphate concentration by 0.10 ± 0.25 mmol/liter
(P < 0.05), whereas solvent alone increased it by
0.35 ± 0.33 mmol/liter in TPTX rats. Infusion of hPTH-(1–84) or
hPTH-(1–34) (1 nmol/h) did not cause a significant decrease in the
serum phosphate concentration compared with that in TPTX animals given
solvent alone. In contrast, all groups infused with hPTH-(7–84)
together with hPTH-(1–84) or hPTH-(1–34) and those infused with the
fragment mixture together with hPTH-(1–34) had significant reductions
of serum phosphate compared with TPTX rats infused with hPTH-(1–84) or
hPTH-(1–34) alone.
|
summarizes the influence of 2-h
infusion of the same PTH preparations on urinary calcium and phosphate
excretion. TPTX reduced urinary phosphate excretion in all groups not
treated with hPTH-(1–84) or hPTH-(1–34), whereas treatment with
hPTH-(1–84) or hPTH-(1–34) increased phosphaturia above levels
observed in sham-operated control rats. hPTH-(7–84) infused with
hPTH-(1–84) or hPTH-(1–34) tended to decrease phosphaturia, but the
results remained nonsignificant due to large variances. TPTX also
tended to reduce calciuria, but the influences of the various PTH
infusion regimens on urinary calcium were less evident.
|
illustrates the
data obtained in ROS 17/2.8 clonal cells. hPTH-(1–84) and hPTH-(1–34)
both increased cAMP production in a dose-dependent manner. hPTH-(1–34)
was slightly more efficient on a molar basis than hPTH-(1–84).
hPTH-(7–84) alone had no influence on cAMP production and did not
reduce the response to hPTH-(1–84) or hPTH-(1–34) (not illustrated).
hPTH-(1–84) and hPTH-(1–34) both displaced the
125I-[Nle8,18,Tyr34]hPTH-(1–34)
tracer from the PTH/PTHrP receptor; hPTH-(1–84) was slightly more
efficient on a molar basis. hPTH-(7–84) at the same molar
concentrations could not displace this tracer. Similar experiments were
performed with
125I-[Tyr34]hPTH-(19–84)
tracer. Binding this time was specific for the C-PTH receptor.
hPTH-(1–84) displaced the tracer from the receptor, whereas
hPTH-(1–34) could not. hPTH-(7–84) was also able to displace the
tracer, but was less potent on a molar basis than hPTH-(1–84).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
To date, few studies have dealt with the modulatory influence of C-fragments on the biological effects of hPTH-(1–84) and hPTH-(1–34) in vivo. PTH-(53–84), when used alone, can stimulate alkaline phosphatase activity in ROS 17/2.8 clonal cells via a C-receptor, but this effect is abolished in the presence of hPTH-(1–34) and/or hPTH-(1–84), which decrease alkaline phosphatase activity via the classic PTH/PTHrP receptor (11, 16, 17, 18). PTH-(3–84), but not PTH-(8–84), has been a potent inhibitor of hPTH-(1–84) bioactivity in renal cytochemical bioassay (38). Furthermore, synthetic C-fragments have been demonstrated to elicit a late response in the same system (39). Bovine PTH-(3–84) (10 nmol/h) infused with bPTH-(1–84) (1 nmol/h) did not suppress the calcemic response to bPTH-(1–84) in TPTX rats, but enhanced urinary cAMP and PO4 excretions relative to hPTH-(1–84) alone (37). Finally, more recently, hPTH-(7–84) has been demonstrated to inhibit the calcemic response to hPTH-(1–84) in TPTX rats maintained on a 0.02% calcium diet (40). It is difficult to reach specific conclusions from these results other than to say that C-fragments can sometimes modulate PTH biological effects via one of the two known PTH receptors.
Our data demonstrate that C-PTH fragments exert a negative control on the Ca2+ concentration, and hPTH-(1–84) or hPTH-(1–34) exert a positive control. This is mainly illustrated by the capacity of hPTH-(7–84) or the fragment mixture (10 nmol/h) infused alone to further reduce the Ca2+ concentration in TPTX rats (negative control) and of hPTH-(1–84) or hPTH-(1–34) (1 nmol/h) to restore the Ca2+ concentration to normal in the same rats (positive control). hPTH-(7–84) or the fragment mixture infused with hPTH-(1–84) or hPTH-(1–34) at the same concentrations in a 10:1 molar ratio produced intermediate Ca2+ concentrations [positive hPTH-(1–84) or hPTH-(1–34) calcemic influence minus negative hPTH-(7–84) or fragment mixture calcemic effect]. These results and those obtained with an intermediate dose of hPTH-(7–84) (3 nmol/h) with hPTH-(1–34) (1 nmol/h) clearly indicate that hPTH-(7–84) exerts a negative control on the Ca2+ concentration. The fragment mixture (10 nmol/h), which contains hPTH-(7–84) (1 nmol/h) and other fragments (9 nmol/h), produced a greater anticalcemic effect than hPTH-(7–84) (3 nmol/h) when infused with hPTH-(1–34) (1 nmol/h), indicating that 9 nmol/h smaller fragments [45% hPTH-(39–84) plus 45% hPTH-(53–84)] exerted a greater anticalcemic action than 2 nmol/h hPTH-(7–84) in the presence of 1 nmol/h PTH-(7–84). This suggests that smaller C-PTH fragments can potentiate the effect of a larger fragment. This is the first time that an anticalcemic effect of several C-fragments has been clearly illustrated in vivo. Our results are similar to those obtained in a recent study in which a hypocalcemic effect of hPTH-(7–84) alone was demonstrated as well as an inhibitory effect of the same molecule on hPTH-(1–84)-induced calcium increase in TPTX rats maintained on a 0.02% calcium diet (40). A molar ratio of hPTH-(1–84) to hPTH-(7–84) of 1:1 was used in that study, much lower than the ratio used in our study, but PTH preparations were also injected ip rather than iv, making any direct comparison difficult.
Clear effects of C-fragments on other aspects of PTH physiology were less evident. Infusion of hPTH-(7–84) alone or with hPTH-(1–84) or hPTH-(1–34) or of the fragment mixture with hPTH-(1–34) reduced the serum phosphate concentration more than hPTH-(1–84) or hPTH-(1–34) alone, indicating that the anticalcemic effect of C-PTH fragments was observed simultaneously with a decrease in serum phosphate. Phosphaturia was diminished in TPTX animals and was greatly increased in all groups treated with either hPTH-(1–84) or hPTH-(1–34). There was a tendency for hPTH-(7–84) to reduce the phosphaturic effect of hPTH-(1–34) in particular, but the results did not reach statistical significance due to large variances. The recent study mentioned above suggested a similar antiphosphaturic action of hPTH-(7–84) injected with hPTH-(1–84) (40). Specific effects on calciuria were not evident, other than a tendency to decrease in all TPTX groups.
To better understand how hPTH-(7–84) exerted its inhibitory influence, we studied its interaction with the classic PTH/PTHrP receptor and the C-PTH receptor, both of which are present on ROS 17/2.8 clonal cells. Both hPTH-(1–84) and hPTH-(1–34) displaced the 125I-[Nle8, 18,Tyr34]hPTH-(1–34) tracer from the classic PTH/PTHrP receptor, whereas hPTH-(7–84) was totally ineffective. Both hPTH-(1–84) and hPTH-(7–84) displaced the 125I-[Tyr34]hPTH-(19–84) recombinant tracer from the C-receptor, with the former preparation being more effective on a molar basis, whereas hPTH-(1–34) caused no displacement. Others have demonstrated that smaller C-PTH fragments do not react with the PTH/PTHrP receptor, and that region 69–84 has to be intact to react with the C-PTH receptor (15). Both hPTH-(1–84) and hPTH-(1–34), in this study as in others, increased cAMP production by ROS 17/2.8 clonal cells (16, 17, 19), whereas hPTH-(7–84) was totally ineffective. This last point was also demonstrated in a recent study (40). These results combined with the effect of hPTH-(39–84) and hPTH-(53–84) in the mixture suggest that the anticalcemic effect of C-PTH fragments may be mediated via the C-PTH receptor. This receptor exists on both osteoblasts (11, 14) and osteocytes (41), and it is possible that C-fragments could act by inhibiting osteocytic osteolysis and/or increasing calcium accretion. The latter point is further sustained by the reduced phosphate levels in serum induced by C-fragments simultaneously with unchanged or slightly decreased phosphaturia compared with hPTH-(1–84) or hPTH-(1–34) alone. These results differ from those obtained with hPTH-(7–34), another PTH inhibitor. The anticalcemic and antiphosphaturic effects of this PTH peptide in vivo were demonstrated at higher molar concentrations and were mediated by an inhibition of hPTH-(1–34) binding to the PTH/PTHrP receptor and of ligand-induced cAMP production (42, 43). This combined with our results illustrated that it is possible to inhibit the biological actions of PTH-(1–84) by blocking its activity at two of the known PTH receptors. Although hPTH-(7–34) appears to exert its inhibitory action by influencing the PTH/PTHrP receptor, hPTH-(7–84) appears mainly to influence the C-PTH receptor.
hPTH-(7–84) and the C-PTH fragment mixture inhibited the calcemic effect of hPTH-(1–34) more readily than that of hPTH-(1–84). This may be related to the fact that hPTH-(1–34) can only interact with the PTH/PTHrP receptor, whereas hPTH-(1–84) can also react with the C-PTH receptor. The C-PTH receptor binds hPTH-(1–84) and could limit the quantity of hormone available to react with the PTH/PTHrP receptor. This is suggested by the fact that the fragment mixture, infused with hPTH-(1–84), caused a greater calcemic response than hPTH-(1–84) alone, possibly by displacing some hPTH-(1–84) from the C-PTH receptor. In this particular case, the fragment mixture’s weaker anticalcemic effect was also masked by binding of hPTH-(1–84) to the C-PTH receptor. Our results are limited by the fact that we used synthetic hPTH fragments that are not identical to those found in the circulation, and obviously we will have to demonstrate that they apply to circulating fragments once their exact nature is known. Nonetheless, our data suggest both positive and negative controls of Ca2+ concentration via hPTH-(1–84) and the PTH/PTHrP receptor, C-PTH fragments, and possibly the C-PTH receptor. This dual control of the Ca2+ concentration would make sense if one looks at the regulation of PTH molecular forms in the circulation by the Ca2+ concentration. Hypocalcemia favors a low C-PTH/I-PTH ratio and thus the positive effects on Ca2+ concentration, whereas hypercalcemia favors a high C-PTH/I-PTH ratio and negative effects on the Ca2+ concentration (1, 5).
The clinical implications of these findings may be important in primary and secondary hyperparathyroidism. In renal failure, non-PTH-(1–84) and other C-PTH fragments accumulate and account for a larger proportion of the circulating PTH (4, 44). This would enhance the inhibitory effect of these fragments on the Ca2+ concentration and stimulate the secretion of more PTH to restore the Ca2+ concentration. Similarly, the amount of non-PTH-(1–84) secreted relative to hPTH-(1–84) could be important to explain why comparable Ca2+ concentrations are often observed with quite different PTH concentrations (6) in patients with primary hyperparathyroidism. More studies are required to elucidate these issues.
Received October 12, 2000.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. J. Felsenfeld, M. Rodriguez, and E. Aguilera-Tejero Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1283 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. Monier-Faugere, H. Mawad, and H. H. Malluche Opposite Effects of Calcitriol and Paricalcitol on the Parathyroid Hormone-(1-84)/Large Carboxy-Terminal-Parathyroid Hormone Fragments Ratio in Patients with Stage 5 Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1255 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Martin and E. A. Gonzalez Metabolic Bone Disease in Chronic Kidney Disease J. Am. Soc. Nephrol., March 1, 2007; 18(3): 875 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jolette, C. E. Wilker, S. Y. Smith, N. Doyle, J. F. Hardisty, A. J. Metcalfe, T. B. Marriott, J. Fox, and D. S. Wells Defining a Noncarcinogenic Dose of Recombinant Human Parathyroid Hormone 1-84 in a 2-Year Study in Fischer 344 Rats Toxicol Pathol, December 1, 2006; 34(7): 929 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Selim, M. Mahon, H. Juppner, F. R. Bringhurst, and P. Divieti Role of calcium channels in carboxyl-terminal parathyroid hormone receptor signaling Am J Physiol Cell Physiol, July 1, 2006; 291(1): C114 - C121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huan, K. Olgaard, L. B. Nielsen, and E. Lewin Parathyroid Hormone 7-84 Induces Hypocalcemia and Inhibits the Parathyroid Hormone 1-84 Secretory Response to Hypocalcemia in Rats with Intact Parathyroid Glands J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1923 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Friedman and W. G. Goodman PTH(1-84)/PTH(7-84): a balance of power Am J Physiol Renal Physiol, May 1, 2006; 290(5): F975 - F984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Arakawa, P. D'Amour, L. Rousseau, J.-H. Brossard, M. Sakai, H. Kasumoto, N. Igaki, T. Goto, T. Cantor, and M. Fukagawa Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 525 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D'Amour, A. Rakel, J.-H. Brossard, L. Rousseau, C. Albert, and T. Cantor Acute Regulation of Circulating Parathyroid Hormone (PTH) Molecular Forms by Calcium: Utility of PTH Fragments/PTH(1-84) Ratios Derived from Three Generations of PTH Assays J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T Potts Parathyroid hormone: past and present J. Endocrinol., December 1, 2005; 187(3): 311 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Divieti, A. I. Geller, G. Suliman, H. Juppner, and F. R. Bringhurst Receptors Specific for the Carboxyl-Terminal Region of Parathyroid Hormone on Bone-Derived Cells: Determinants of Ligand Binding and Bioactivity Endocrinology, April 1, 2005; 146(4): 1863 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Murray, L. G. Rao, P. Divieti, and F. R. Bringhurst Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl- Terminal Ligands Endocr. Rev., February 1, 2005; 26(1): 78 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D'Amour, J.-H. Brossard, A. Rakel, L. Rousseau, C. Albert, and T. Cantor Evidence That the Amino-Terminal Composition of Non-(1-84) Parathyroid Hormone Fragments Starts before Position 19 Clin. Chem., January 1, 2005; 51(1): 169 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hayashi, Y. Tsuchiya, Y. Itaya, T. Takenaka, K. Kobayashi, M. Yoshizawa, R. Nakamura, T. Monkawa, and A. Ichihara Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial Nephrol. Dial. Transplant., August 1, 2004; 19(8): 2067 - 2073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Kazama, K. Omori, N. Higuchi, N. Takahashi, Y. Ito, H. Maruyama, I. Narita, T. L. Cantor, P. Gao, and F. Gejyo Intact PTH assay overestimates true 1-84 PTH levels after maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism Nephrol. Dial. Transplant., April 1, 2004; 19(4): 892 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Bringhurst Circulating Forms of Parathyroid Hormone: Peeling Back the Onion Clin. Chem., December 1, 2003; 49(12): 1973 - 1975. [Full Text] [PDF]
|
|
|
|
|
|
P. D'Amour, J.-H. Brossard, L. Rousseau, L. Roy, P. Gao, and T. Cantor Amino-Terminal Form of Parathyroid Hormone (PTH) with Immunologic Similarities to hPTH(1-84) Is Overproduced in Primary and Secondary Hyperparathyroidism Clin. Chem., December 1, 2003; 49(12): 2037 - 2044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Hodsman, D. A. Hanley, M. P. Ettinger, M. A. Bolognese, J. Fox, A. J. Metcalfe, and R. Lindsay Efficacy and Safety of Human Parathyroid Hormone-(1-84) in Increasing Bone Mineral Density in Postmenopausal Osteoporosis J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5212 - 5220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Silverberg and J. P. Bilezikian "Incipient" Primary Hyperparathyroidism: A "Forme Fruste" of an Old Disease J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5348 - 5352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Silverberg, P. Gao, I. Brown, P. LoGerfo, T. L. Cantor, and J. P. Bilezikian Clinical Utility of an Immunoradiometric Assay for Parathyroid Hormone (1-84) in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4725 - 4730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Estepa, I. Lopez, A. J. Felsenfeld, P. Gao, T. Cantor, M. Rodriguez, and E. Aguilera-Tejero Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1101 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Reichel, A. Esser, H.-J. Roth, and H |
). B and C, All groups infused with hPTH-(1–84) or hPTH-(1–34),
respectively, are illustrated, and comparisons are made with the
hPTH-(1–84) or -(1–34) alone group (
), hPTH-(1–34)
(
), and hPTH-(7–84) (•) on cAMP production (A) and displacement
of 125I-[Nle8,18,Tyr
34]hPTH-(1–34) tracer from the PTH/PTHrP receptor (B) and
of 125I-[Tyr34]hPTH-(19–84) tracer from the
carboxyl-PTH receptor (C) in ROS17–2.8 clonal cells. Results are the
mean ± SD of four or five (A) or two (B and C)
different experiments conducted in triplicate. Statistical analysis was
performed by one-way ANOVA, followed by Student-Newman-Keuls test. A,
Results obtained with hPTH-(7–84) are compared with those of the two
other PTH preparations; B, again, results with hPTH-(7–84) are
compared with those of the two other PTH preparations; C, results
obtained with hPTH-(1–34) are compared with those of the two other PTH
preparations. ++, P < 0.01; +++,
P < 0.001.