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PubMed1974

Secretion of parathyroid hormone in patients with medullary thyroid carcinoma.

The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor.

Calcitonin↗
PubMed2000

The influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats.

The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-month-old ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 microg/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH(1-34) alone. Both PTH(1-34) alone and rhGH alone increased the mechanical strength of the femoral diaphysis, and further increase in mechanical strength resulted from combined PTH(1-34) plus rhGH treatment. OVX by itself induced the characteristic increase in medullary cavity cross-sectional area and a minor decrease in the mechanical quality of the osseous tissue.

Age Factors↗
PubMed1989

Parathyroid hormone regulation of proline uptake by cultured neonatal mouse osteoblastlike cells.

Regulation of proline uptake by the synthetic amino-terminal fragment of bovine parathyroid hormone [bPTH-(1-34)] has been studied in confluent primary cultures of osteoblastlike cells isolated from neonatal mouse calvaria. The initial velocity of proline transport was increased by 85% in cultures treated with 24 nM bPTH-(1-34) for 6 h. Cycloheximide, at a concentration that inhibited protein synthesis by 97%, did not prevent this effect. However, adding the inhibitor during the first 1-2 h of hormone treatment did significantly reduce its magnitude. Exposure of cells to the inhibitor alone caused a time-dependent decrease in the basal rate of proline uptake. In the absence of protein synthesis, the maximal velocity (Vmax) of transport was 60% greater in cultures treated with 24 nM bPTH-(1-34) than in controls. The concentration of proline at which half-maximal transport occurred (Km) was unchanged. In cultures treated with cycloheximide alone, proline transport decreased as a first-order exponential with a half-life of 250-280 min. Parathyroid hormone significantly reduced this decline, increasing the half-life of proline transport activity about fourfold. These effects were duplicated by 1 mM DBcAMP. It is concluded that bPTH-(1-34) increases proline transport in osteoblastlike cells by decreasing the degradation of amino acid transport system A proteins. The hormone may also affect the synthesis of these molecules. These effects appear to be mediated by cAMP.

Animals↗
PubMed1994

Effects of parathyroid hormone depletion in dogs with induced renal failure.

Six parathyroidectomized (PTX) and 6 control dogs had renal mass reduced by 15/16, and were studied for effects of parathyroid hormone depletion on progression of renal failure. All PTX dogs and 4 of 6 control dogs survived until necropsy after 32 weeks. Plasma parathyroid hormone concentration was undetectable in PTX dogs throughout the study, but was greater than normal in control dogs. Serum inorganic phosphate (P) concentration was increased in PTX dogs (6.8 +/- 0.1 mg/dl) and in control dogs (7.5 +/- 0.2), but did not differ significantly (P = 0.254) between groups. Ionized blood calcium values (Ca2+) were significantly (P = 0.014) lower in PTX dogs (1.31 +/- 0.01 mmol/L) than in control dogs (1.36 +/- 0.00 mmol/L), but were more variable in PTX dogs. Values in PTX dogs were not significantly different from those in control dogs for glomerular filtration rate (P = 0.914), plasma creatinine concentration (P = 0.903), and urine protein to creatinine ratio (P = 0.756) determined at intervals during the study. Terminal glucose tolerance and plasma insulin concentrations, P tolerance, and renal P excretion did not differ between groups. Histologic comparison of kidneys removed during reduction of renal mass with kidneys removed at necropsy revealed development of lesions in both groups of dogs, and no protective effect from parathyroidectomy. Mineral analysis of aorta, brain, heart, lungs, and skeletal muscle obtained at necropsy revealed no significant difference between PTX and control groups. Renal cortical calcium concentration was significantly (P < 0.05) greater in kidneys obtained at necropsy then in kidneys obtained during nephrectomy, but PTX did not protect renal cortex from calcium deposition.

Animals↗
PubMed1977

Degradation of parathyroid hormone and fragment production by the isolated perfused dog kidney. The effect of glomerular filtration rate and perfusate CA++ concentrations.

The renal degradation of intact bovine parathyroid hormone (b-PTH 1-84) was studied with the isolated perfused dog kidney. Disappearance of b-PTH 1-84 from the perfusate occurred concomitantly with the appearance of smaller molecular weight forms of immunoreactive parathyroid hormone (PTH). These smaller molecular weight PTH fragments included both carboxyl and amino terminal regions of the PTH peptide. Perfusate from kidneys with lower glomerular filtration rates (GFR) contained b-PTH 1-84 for longer periods of time than kidneys with higher GFRs, and perfusate from kidneys with lower GFRs demonstrated greater accumulation of carboxyl terminal PTH fragments. Perfusate containing high Ca++ concentrations retarded, and perfusate with low Ca++ concentrations accelerated the rate of degradation of b-PTH 1-84 by the kidney. These studies, therefore document the production of PTH fragments during the course of intact hormone degradation by the kidney. They also demonstrate renal clearance of the PTH fragments produced and define the effects of glomerular filtration rate and calcium concentrations on degradation of intact hormone and the clearance of PTH fragments.

Animals↗
PubMed1980

In vitro activation of adenylate cyclase by norepinephrine, parathyroid hormone, calcitonin, and prostaglandins in the developing maxillary process and palatal shelf of the golden hamster.

The regional localization of hormonally sensitive adenylate cyclase within the maxillary-palatal process complex was examined in tissue homogenates at different stages during the development of the secondary palate in the golden hamster. The most potent agents capable of activating adenylate cyclase were parathyroid hormone (PTH) and calcitonin (CT). Highest activities were observed in the intact maxillary process-palatal shelf complex and the isolated maxillary process prior to and during fusion of the palate. Thereafter, neither hormone displayed a remarkable capacity to elevate enzyme activity. Parathyroid hormone and CT exhibited a similar, but considerably reduced, capacity for enzyme stimulation in the isolated palatal shelf. 1'-Norepinephrine also increased adenylate cyclase activity in both the palatal shelf and the maxillary process at the earlier stages. Prostaglandins (PG) E1, E2, and F2 alpha stimulated adenylate cyclase activity within the intact palate, the maxillary process, and the palatal shelf primarily at the earlier stages. The adenylate cyclase from the isolated palatal shelf was more sensitive to stimulation by the PGs than that from either the intact palate samples or isolated maxillary processes. The findings imply that the fusion process of the secondary palate is under a highly sensitive hormonal control mechanism.

Adenylyl Cyclases↗
PubMed1978

[Parathyroid hormone and 25-hydroxycholecalciferol concentrations in the serum of patients with kidney transplantations and their radiological correlation].

In 40 renal transplant patients the serum concentration of parathyroid hormone, 25-hydroxycholecalciferol, calcium and inorganic phosphate were estimated. The results of these biochemical studies were compared to X-ray soft tissue and bone pathologic findings. The serum immunoreactive parathyroid hormone (iPTH) was normal in 37 patients and increased in 3 cases. 19 (47.5%) renal transplant recipients showed decreased serum 25-hydroxycholecalciferol levels. In 23 out of 40 patients (57.5%) serum phosphate was lower than 3.0 mg/100 ml. X-ray soft tissue changes were observed in 28 (70%) and bone changes in 18 (45%) patients; both frequencies were higher when compared to occurrence during regular dialysis treatment. Features of hyperparathyroid osteopathy were frequently observed in renal transplant recipients. Femoral head necroses were predominant in men, whereas osteomalacia with Looser's zones were found mainly in women. The pathogenesis of X-ray bone changes in patients with renal transplants seems to be multifactorial and related to the duration of secondary hyperparathyroidism before renal transplantation as well as to phosphate depletion and 25-hydroxycholecalciferol deficiency.

Adult↗
PubMed2006

Parathyroid surgical failures with sufficient decline of intraoperative parathyroid hormone levels: unobserved multiple endocrine neoplasia as an explanation.

HYPOTHESIS: A sufficient decline in levels of parathyroid hormone measured intraoperatively (ioPTH) precludes early and late surgical failures. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with ioPTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: Two hundred sixty-nine consecutive patients with sporadic primary hyperparathyroidism who underwent first-time parathyroid surgery with ioPTH measurement were followed up for as long as 10 years after surgery. Data on all patients have been collected in a prospective database. MAIN OUTCOME MEASURES: Surgical failures up to 10 years after parathyroid surgery. RESULTS: With an average follow-up of 3.6 years (range, 6-120 months), the overall cure rate was 96%. The ioPTH level correctly predicted long-term outcome in 248 (92%) of 269 patients. Six patients had a false-positive ioPTH finding. Five of these patients were found to have germline mutations in the gene for multiple endocrine neoplasia. The remaining patient has not undergone genetic testing. The mutations have rarely (n = 1) or never (n = 4) been described before, to our knowledge. CONCLUSIONS: Intraoperative measurement of PTH level has a high overall accuracy with a mean follow-up of 3.6 years. However, among the late surgical failures with false-positive ioPTH findings, overlooked mutations in the multiple endocrine neoplasia gene should be suspected, and therefore genetic analyses in these patients are of great importance.

Adenoma↗
PubMed1989

Elevated serum intact parathyroid hormone levels in elderly patients with hip fracture.

It has been postulated that secondary hyperparathyroidism contributes to bone loss and the high incidence of hip fractures in the elderly population, but there are no data on serum intact parathyroid hormone concentrations in these patients. In this study, serum intact parathyroid hormone (PTH) levels have been measured in 39 elderly patients with hip fracture; in addition, serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 concentrations have been measured. Twenty patients (51.3%) had elevated serum intact PTH concentrations whilst five (12.8%) had abnormally low serum 25-hydroxyvitamin D3 levels and serum 1,25-dihydroxyvitamin D3 was reduced in only two. These results provide the first direct evidence for secondary hyperparathyroidism in elderly patients with hip fracture. Vitamin D deficiency is unlikely to be the sole cause of secondary hyperparathyroidism in these subjects and calcium deficiency by itself may also contribute.

Aged↗
PubMed1985

Identification of a 150-kDa membrane component which is modulated by parathyroid hormone.

Monoclonal antibodies have been produced against primary bone cells obtained from the collagenase digestion of mouse cranial bone. Antibodies were selected on the basis of their immunoglobulin class and those which were identified as IgG were further screened for their ability to inhibit cAMP accumulation in response to sub-maximal doses of the 1-34 amino-terminal peptide of bovine parathyroid hormone, bPTH(1-34). Nine hybridoma clones were subsequently characterized as inhibitory with respect to parathyroid hormone (PTH) responses in intact mouse cranial bone and which also identified a variety of membrane components from detergent extracts of surface-labeled primary bone cells. Five of these antibodies immunoprecipitated a membrane component with Mr of 80 000 that appeared to be a major component of the extract susceptible to surface-labeling with 125I. All nine monoclonal antibodies were shown to bind to a suspended-cell preparation of primary bone cells with 2-3 orders of magnitude greater binding than that of control antibodies. Using this assay, one clone, designated 3G12 IgG, was observed to exhibit desensitization effects at the binding level with a time course and dose dependency for PTH pre-incubation that was similar to the establishment of the refractory state in other systems. In addition, the desensitization effect occurred at 37 degrees C but not at 4 degrees C. This antibody was shown to bind saturably to both intact mouse cranial bone and primary bone cells with an apparent affinity constant (Ka) in the range of 10(9) M. Inhibition of bone cAMP accumulation in response to 2.5 nM bPTH(1-34) was directly correlated to the binding of 3G12 IgG to intact mouse calvariae. A maximum inhibition of approximately 85% was observed. 3G12 IgG immunoprecipitated a single membrane component, Mr 150 000, from NP-40 detergent extracts of 125I-labeled primary mouse bone cells. The molecular mass of this component was also 150 000 daltons when run on polyacrylamide gel slabs under non-reducing conditions. Control and PTH-pre-treated bone cells were surface-labeled, detergent-solubilized and immunoprecipitated with 3G12 IgG in order to investigate further the desensitization effect at the molecular level. Incubation of bone cells with 1 microgram/ml bPTH(1-34) for 45 min at 37 degrees C caused an increased susceptibility to surface-labeling with 125I that was approximately three-fold higher in specific activity than that of control cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

In vivo regulation of apoptosis in metaphyseal trabecular bone of young rats by synthetic human parathyroid hormone (1-34) fragment.

Osteoblast differentiation and function can be studied in situ in the metaphysis of growing long bones. Proliferation and apoptosis dominate in the primary spongiosa subjacent to the growth plate, and differentiation and function dominate in the proximal metaphysis. Apoptosis of osteocytes dominates at the termination of the trabeculae in diaphyseal marrow. As parathyroid hormone regulates all phases of osteoblast development, we studied the in vivo regulation by human parathyroid hormone (1-34) (PTH) of apoptosis in bone cells of the distal metaphysis of young male rats. Rats were given PTH at 80 microg/kg per day, once daily, for 1-28 days. Bone cells were defined for flow cytometry as PTH1-receptor-positive (PTH1R(+)) and growth factor-receptor-positive (GFR(+)) cells. Apoptotic cells stained positive for either TdT-mediated dUTP-X nick end labeling (TUNEL) or annexin V (annV(+)) were detected by either flow cytometry or immunohistochemistry. Apoptosis was also assessed at the tissue level by RNAse protection and caspase enzyme activity assays. PTH increased apoptotic osteoblasts in the proliferating zone and apoptotic osteocytes in the terminal trabecular zone, by 40%-60% within 2-6 days of PTH treatment, but values became equivalent to controls after 21-28 days of treatment. This transient increase was confirmed in PTH1R(+), GFR(+) bone cells isolated by flow cytometry. There was no detectable change in the steady-state mRNA levels of selected apoptotic genes. Starting at 3 days, at the tissue level, PTH inhibited activity of caspases, which recognize the DEVD peptide substrate (caspases 2, 3, and/or 7), but not those caspases recognizing LEHD or YVAD peptide sequences. We speculate that the localized and tissue level effects of PTH on apoptosis can be explained on the basis of its anabolic effect on bone. The transient increase in apoptosis in the proliferating zone and terminal trabecular zone may be the result of the increased activation frequency and bone turnover seen with daily PTH treatment. As once-daily PTH increases the number of differentiated osteoblasts, and as these and hematopoietic marrow cells dominate metaphyseal tissue, inhibition of caspase activity may contribute to their prolonged survival, enabling extension of trabecular bone into the diaphyseal marrow to increase bone mass.

Age Factors↗
PubMed2001

Parathyroid hormone receptor internalization is independent of protein kinase A and phospholipase C activation.

Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) binding to their common receptor stimulates second messenger accumulation, receptor phosphorylation, and internalization. LLC-PK(1) cells expressing a green fluorescent protein-tagged PTH/PTHrP receptor show time- and dose-dependent receptor internalization. The internalized receptors colocalize with clathrin-coated pits. Internalization is stimulated by PTH analogs that bind to and activate the PTH/PTHrP receptor. Cell lines expressing a mutant protein kinase A regulatory subunit that is resistant to cAMP and/or a mutant receptor (DSEL mutant) that does not activate phospholipase C internalize their receptors normally. In addition, internalization of the wild-type receptor and the DSEL mutant is stimulated by the PTH analog [Gly(1),Arg(19)]hPTH-(1-28), which does not stimulate phospholipase C. Forskolin, IBMX, and the active phorbol ester, phorbol-12-myristate-13-acetate, did not promote receptor internalization or increase PTH-induced internalization. These data indicate that ligand-induced internalization of the PTH/PTHrP receptor requires both ligand binding and receptor activation but does not involve stimulation of adenylate cyclase/protein kinase A or phospholipase C/protein kinase C.

1-Methyl-3-isobutylxanthine↗
PubMed1989

The importance of parathyroid hormone in inhibition of collagen synthesis and mitogenesis of osteoblastic cell.

Loss of bone substance is a common manifestation of hyperparathyroidism. This suggests that parathyroid hormone (PTH) plays an important role as to bone mass. To investigate the mechanism underlying this change in bone mass, I studied the effects of PTH on collagen synthesis and mitogenesis of UMR-106 rat osteoblastic osteosarcoma cells. PTH inhibits the mitogenesis of UMR-106 rat osteosarcoma cells, the half-maximal concentration being 10(-8) to 10(-7) M, which is similar to the EC50 for cyclic AMP accumulation. Cyclic AMP, whose intracellular concentration was increased by PTH, plays a role in the modulation of mitogenesis, as shown by the comparable inhibitory effects of 8-bromoadenosine-3',5'-cyclic AMP (10(-4) M), forskolin (10(-7) M), and the phosphodiesterase inhibitor, IBMX (10(-5) M). PTH, in a similar concentration range, directly inhibited collagen synthesis. Concurrent with the suppression of collagen synthesis, the amounts of a1(I) and a2(I) collagen mRNA decreased proportionately. The results show that PTH modulates collagen synthesis at the transcriptional level. I concluded that parathyroid hormone inhibits the mitogenesis of osteoblasts as well as collagen synthesis by these cells. The decreases in the number of osteoblasts and the amount of collagen synthesis contribute to the loss of bone substance in hyperparathyroidism.

Animals↗
PubMed1999

Calcium bioavailability and parathyroid hormone acute changes after oral intake of dairy and nondairy products in healthy volunteers.

This study was designed to compare calcium bioavailability and serum parathyroid hormone acute changes after oral intake of 500 mg of elemental calcium from liquid milk, yogurt, calcium-citrate-enriched powdered milk or a calcium carbonate pill; or after intake of soybean imitation-milk. After a 12-h fast, blood samples were drawn both at baseline and 1, 2, 3 and 4 h after an oral intake of the above-mentioned products, which were ingested together with a light neutral breakfast. The administration order of the study products was randomly assigned to each of 19 healthy young volunteers (11 females, 8 males). The baseline serum concentrations of ionized calcium, phosphorus and intact parathyroid hormone (iPTH) were normal. Calcium-citrate-enriched powdered milk induced a significant increase in serum ionized calcium (p<0.001) and a significant and continuous decrease in serum iPTH concentration (p<0. 001). Yogurt and the calcium carbonate pill induced a similar but less significant effect, increasing serum ionized calcium (p<0.05) and decreasing serum iPTH (p<0.01). Liquid milk only induced a significant change in serum ionized calcium and iPTH concentration during the first 2 h; this effect was lost during the following 2 h. In conclusion, our study suggests the possibility that the addition of calcium citrate to powered milk may improve calcium bioavailability and enhance the inhibitory effect on serum iPTH in the assayed conditions.

Adult↗
PubMed1998

Binding domain of human parathyroid hormone receptor: from conformation to function.

A 31 amino acid fragment of the extracellular N-terminus of the human G-protein coupled receptor for parathyroid hormone (PTH1R) has been structurally characterized by NMR and molecular dynamics simulations. The fragment PTH1R[168-198] includes residues 173-189, shown by photoaffinity cross-linking to be a contact domain with position 13 of parathyroid hormone (PTH). The structure of PTH1R[168-198], determined in a micellar solution of dodecylphosphocholine to mimic the membrane environment, consists of three alpha-helices, separated by a well-defined turn and a flexible region. The topological orientation of PTH1R[168-198] was determined from nitroxide-radical induced relaxation of NMR signals utilizing 5- and 16-doxylstearic acid. The C-terminal helix (residues 190-196), consisting of seven amino acids of the first transmembrane domain, is very hydrophobic and embedded in the lipid core. This helix is preceded by a well-defined turn, forming an approximate 90 degrees bend, placing the other helices (residues 169-176 and 180-189), both of which are amphipathic, on the surface of the micelle. In this orientation, many hydrophilic residues of the receptor, including Glu177, Arg179, Arg181, Glu182, Asp185, and Arg186, are projecting toward the solvent available to form complementary Coulombic interactions with the polar residues of the principal binding domain of the ligand (e.g., Arg25, Lys26, Lys27, Asp30, and His32). Given that the binding domain of PTH adopts an amphipathic alpha-helix which lies on the membrane, we visualize ligand binding as a two stage process involving a nonspecific hydrophobic interaction of amphipathic helices with the membrane, followed by two-dimensional diffusion leading to highly specific, ligand-receptor interaction.

Amino Acid Sequence↗
PubMed1992

Acute effect of dialysate calcium concentration and intravenous vitamin D3 on the secretion of parathyroid hormone in hemodialysis patients.

We studied the suppression of intact parathyroid hormone (PTH) in ten patients on chronic hemodialysis using different calcium concentrations of dialysate. Secondly, giving i.v. vitamin D3 at commencement of dialysis we investigated whether 1 alpha (OH)D3 or 1,25(OH)2D3 acutely modifies the responsiveness of the parathyroid gland to the suppressive effect of increased serum calcium. Dialysis with high-calcium dialysate (1.75 mmol/l) reverted the plasma PTH to normal limits. Lower-calcium dialysate (1.5 mmol/l) induced only a partial suppression of hyperparathyroidism. We found no differences in the suppression of hyperparathyroidism whether 1 alpha (OH)D3 or 1,25(OH)2D3 was given at the beginning of the dialysis or not. We conclude that the suppressibility of hyperparathyroidism in dialysis patients can be evaluated by different calcium concentrations of dialysate, and that i.v. vitamin D3 does not acutely modify the responsiveness of the parathyroid gland to the effect of calcium.

Aged↗
PubMed1984

Peripheral metabolism of parathyroid hormone in patients with primary hyperparathyroidism as judged by immunological and biological studies.

The present study characterizes the immunological and biological activity of circulating forms of parathyroid hormone (PTH) in patients with primary hyperparathyroidism. In addition, the rate of elimination of intravenously injected 125I-labelled bovine parathyroid hormone (125I-bPTH) was studied in patients with this disease before and after operation. The different molecular forms of serum PTH were characterized by gel chromatography followed by radioimmunoassay employing two antisera with specificities directed against the N-terminal and mid-region part of the peptide, respectively. The major part of immunoreactive PTH (iPTH; on the average above 50%) eluted corresponding to fragments with a molecular size about 7,500 daltons in both radioimmunoassays. Specific immunoreactivity coeluting with the intact hormone represented 9-15%. The biological activity of hyperparathyroid serum after gel chromatography was tested in a hormone-sensitive rat kidney adenylyl cyclase assay system. The basal and PTH-stimulated adenylyl cyclase activity (half-maximal) stimulation at 5 micrograms/l or 0.6 nM) was dependent on Mg2+ and ATP. Maximal responses to PTH, calcitonin, and prostaglandin E2 were 50-200% above basal activity and were obtained in the presence of both GTP and Gpp(NH)p (5 X 10(-4) M). Serum from patients with hyperparathyroidism and PTH extracted from parathyroid tissue stimulated the adenylyl cyclase in a dose-dependent manner, as did the chromatographic fraction representing the intact hormone. Elimination of 125I-bPTH from circulation after intravenous injection to patients with this disease suggested that the hormone, but not its degradation products, were removed more rapidly before than after successful surgery. We conclude that the major part of circulating iPTH in patients with primary hyperparathyroidism is unable to stimulate the rat kidney adenylyl cyclase, and that the biological PTH activity is represented by the intact hormone (15% or less of total iPTH). These patients degrade more rapidly the injected 125I-bPTH and this mechanism introduces a new concept to protect target cells against excessive hormone action.

Adenylyl Cyclases↗
PubMed1997

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism.

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.

Adolescent↗