Parathyrin radioimmunoassay: diagnostic utility of antisera produced against carboxyl-terminal fragments of the hormone from the human.

Abstract Antisera directed toward the carboxyl-terminal region of human parathyrin (parathyroid hormone), for use in daignostically applicable radioimmunoassays of the hormone in serum, are scarce, largely because of the lack of suitable immunogens of human origin. We produced four antisera in goats and guinea pigs by immunization with recently discovered carboxyl-terminal fragments of human parathyrin extracted from parathyroid tumors. Here, we report results of radioimmunoassays of nearly 200 normal and pathological sera with one of these antisera; we observed almost complete differentiation between concentrations of parathyrin in serum of healthy normal subjects and patients with primary, secondary (due to chronic renal failure), or "ectopic" hyperparathyroidism (due to nonparathyroid cancer). The availability of a new immunogen should now make possible the deliberate production of large quantities of diagnostically applicable parathyrin antisera directed toward the carboxyl-terminal region of human parathyrin. This should, in turn, lead to more widespread availability of this useful radioimmunoassay.

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Parathyroid hormone inhibits B cell proliferation: implications in chronic renal failure.

Journal of the American Society of Nephrology ◽

10.1681/asn.v13236 ◽

1990 ◽

Vol 1 (3) ◽

pp. 236-244

Author(s):

J M Alexiewicz ◽

M Klinger ◽

T O Pitts ◽

Z Gaciong ◽

M Linker-Israeli ◽

...

Keyword(s):

Cell Proliferation ◽

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

B Cells ◽

B Cell ◽

Normal Subjects ◽

Dependent Manner ◽

Dialysis Patients ◽

Amino Terminal

B cell proliferation is impaired in patients with chronic renal failure, but the mechanisms underlying this defect are not known. Lymphocytes have receptors for parathyroid hormone, and it is possible that the state of secondary hyperparathyroidism of renal failure is responsible for the B cell defect. Our studies were designed to (a) examine T cell-independent B cell proliferation [3H)thymidine incorporation) induced by Staphylococcus aureus Cowan 1 after 5 days of culture, (b) evaluate the effect of parathyroid hormone on S. aureus Cowan I-induced B cell proliferation, and (c) investigate the mechanisms through which parathyroid hormone may exert its effect on B cell proliferation. Lymphocytes were obtained from 37 normal subjects and 21 dialysis patients. S. aureus Cowan I induced significant stimulation (P less than 0.01) of the proliferation of B cells from both groups, but the effect was smaller on B cells from dialysis patients (10.0 x 10(3) +/- 1.4 x 10(3) cpm) than on those from normal subjects (21.8 x 10(3) +/- 2.0 x 10(3) cpm). Both the intact molecule of parathyroid hormone (1-84 PTH) and its amino-terminal fragment (1-34 PTH) caused significant inhibition of proliferation of B cells from normal subjects in a dose-dependent manner, with the effect being significantly greater (P less than 0.01) with an equimolar concentration of 1-84 PTH than that of 1-34 PTH. Inactivation of 1-84 PTH by oxidation abolished most of its inhibitory effect on B cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Distribution of Circulating Immunoreactive Components of Parathyroid Hormone in Normal Subjects and in Patients with Primary and Secondary Hyperparathyroidism: The Role of the Kidney and of the Serum Calcium Concentration

Clinical Science ◽

10.1042/cs0570435 ◽

1979 ◽

Vol 57 (5) ◽

pp. 435-443 ◽

Cited By ~ 28

Author(s):

M. A. Dambacher ◽

J. A. Fischer ◽

W. H. Hunziker ◽

W. Born ◽

J. Moran ◽

...

Keyword(s):

Vitamin D ◽

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Primary Hyperparathyroidism ◽

Vitamin D Deficiency ◽

Normal Subjects ◽

Dependent Manner ◽

Intact Pth ◽

Calcium Dependent

1. The distribution of intact parathyroid hormone-(1–84) [PTH-(1–84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1–84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000–7000 (peak II) and immunoreactive components co-eluting with human PTH-(1–12) (peak III) were observed. 2. Mean concentrations of intact PTH-(1–84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1–84). 3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1–84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.

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Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647030 ◽

1988 ◽

Vol 60 (02) ◽

pp. 205-208 ◽

Cited By ~ 21

Author(s):

Paul A Kyrle ◽

Felix Stockenhuber ◽

Brigitte Brenner ◽

Heinz Gössinger ◽

Christian Korninger ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Blood Clotting ◽

Normal Subjects ◽

Chronic Uraemia ◽

Wall Interaction ◽

End Stage ◽

Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

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Parathyroid hormone secretory function and serum levels of carboxyl-terminal flanking peptide (PDN-21) of the human calcitonin gene in normal subjects and osteoporotic patients

Acta Endocrinologica ◽

10.1530/acta.0.111s185 ◽

1986 ◽

Vol 113 (1_Suppl) ◽

pp. S185-S186

Author(s):

J. ITTNER ◽

M.A. DAMBACHER ◽

R. MUFF ◽

J.A. FISCHER

Keyword(s):

Parathyroid Hormone ◽

Normal Subjects ◽

Serum Levels ◽

Human Calcitonin ◽

Secretory Function ◽

Calcitonin Gene ◽

Carboxyl Terminal

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Role of parathyroid hormone in the glucose intolerance of chronic renal failure.

Journal of Clinical Investigation ◽

10.1172/jci111765 ◽

1985 ◽

Vol 75 (3) ◽

pp. 1037-1044 ◽

Cited By ~ 99

Author(s):

M Akmal ◽

S G Massry ◽

D A Goldstein ◽

P Fanti ◽

A Weisz ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Glucose Intolerance

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Parathyroid hormone secretion in chronic renal failure

Kidney International ◽

10.1038/ki.1996.488 ◽

1996 ◽

Vol 50 (5) ◽

pp. 1700-1705 ◽

Cited By ~ 2

Author(s):

Jesper C. Madsen ◽

Anne Q. Rasmussen ◽

Søren D. Ladefoged ◽

Peter Schwarz

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Hormone Secretion

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Parathyroid hormone metabolism and its potential as a uremic toxin

AJP Renal Physiology ◽

10.1152/ajprenal.1980.239.1.f1 ◽

1980 ◽

Vol 239 (1) ◽

pp. F1-F12 ◽

Cited By ~ 3

Author(s):

E. Slatopolsky ◽

K. Martin ◽

K. Hruska

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Biological Effects ◽

Uremic Toxin ◽

Terminal Portion ◽

Single Chain ◽

Biochemical Alterations ◽

Amino Terminal ◽

Carboxy Terminal

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a “uremic toxin” responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant “uremic toxin.”

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Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Clinical Science ◽

10.1042/cs0960427 ◽

1999 ◽

Vol 96 (4) ◽

pp. 427-430 ◽

Cited By ~ 4

Author(s):

M. BLUM ◽

Y. WEISMAN ◽

S. TURGEMAN ◽

S. CABILI ◽

Y. WOLLMAN ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Virgin Female ◽

Normal Pregnancy ◽

High Serum ◽

Female Rats ◽

Pregnant Rats ◽

Serum Ipth ◽

Immunoreactive Parathyroid Hormone

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

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