Circulating levels of biologically active parathyroid hormone in rheumatic diseases.

Abstract Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and hypoparathyroidism. The move to two-site immunometric assays that detect the whole molecule has improved the discrimination of these conditions but these assays may be too restrictive because some PTH fragments that are biologically active may not be detected. In addition, PTH-like peptide of malignancy, an important cause of malignancy-associated hypercalcaemia, is not detected by the two-site assays. Experiments were performed to set up a simple, robust and inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP or an eluted stain assay as the end point. Of the 12 cell lines tested, an opossum kidney (WOK) cell line showed the most promise. Despite optimization of the procedure to include pre-treatment with dexamethasone, insulin and PTH, followed by incubation in the presence of 5′ -guanylimidodiphosphate, isobutyl-1-methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for use in a cultured cell bioassay for PTH in human serum. In addition, the cells were less sensitive to PTH-like peptide precluding their use for an assay for this molecule. Journal of Endocrinology (1994) 143, 261–268

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BIOLOGICALLY ACTIVE PARATHYROID HORMONE IN FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA

Clinical Endocrinology ◽

10.1111/j.1365-2265.1984.tb03472.x ◽

1984 ◽

Vol 21 (3) ◽

pp. 293-298 ◽

Cited By ~ 16

Author(s):

J. ALLGROVE ◽

A. K. SANGAL ◽

D. C. LOW ◽

P. H. WELLER ◽

N. LOVERIDGE

Keyword(s):

Parathyroid Hormone ◽

Biologically Active

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Effects of dDAVP on rat juxtamedullary nephrons: stimulation of medullary K recycling

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.2.f291 ◽

1985 ◽

Vol 249 (2) ◽

pp. F291-F298 ◽

Cited By ~ 2

Author(s):

J. M. Elalouf ◽

N. Roinel ◽

C. de Rouffignac

Keyword(s):

Parathyroid Hormone ◽

Adenylate Cyclase ◽

Excretion Rate ◽

Distal Tubule ◽

Fractional Excretion ◽

The Other ◽

Thick Ascending Limb ◽

Adenylate Cyclase System ◽

Circulating Levels ◽

Stimulation Of

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on the handling of water and electrolytes by the juxtamedullary nephrons were studied on rats with reduced circulating levels of antidiuretic hormone (ADH), parathyroid hormone, calcitonin, and glucagon, all of which stimulate the adenylate cyclase system of the thick ascending limb and the distal tubule. In such hormone-deprived rats and in hormone-deprived + dDAVP rats, the concentration of Na, Cl, and total solutes was lower in the ascending than in the descending limbs, whereas the inulin concentration was similar at both sites. dDAVP did not alter the fraction of NaCl remaining in the thin limbs, but tended to reduce that of Mg and Ca. On the other hand, dDAVP significantly increased the fraction of filtered K remaining from 65.8 +/- 5.2 to 107.3 +/- 15.8%. A direct correlation was observed between the fraction of filtered K remaining at the tip of the juxtamedullary loops and the fractional excretion rate of K in urine. Since dDAVP enhances distal K net secretion, as previously shown in our laboratory, these results indicate that the medullary recycling of K from nephron terminal segments to Henle's loop of juxtamedullary nephrons is stimulated by this peptide.

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Nesfatin-1-like peptide suppresses hypothalamo–pituitary–gonadal mRNAs, gonadal steroidogenesis, and oocyte maturation in fish†

Biology of Reproduction ◽

10.1093/biolre/ioaa106 ◽

2020 ◽

Vol 103 (4) ◽

pp. 802-816

Author(s):

Jithine Jayakumar Rajeswari ◽

Azadeh Hatef ◽

Suraj Unniappan

Keyword(s):

Oocyte Maturation ◽

Reproductive Hormones ◽

Reproductive Physiology ◽

Biologically Active ◽

Metabolic Effects ◽

Steroidogenic Enzyme ◽

Male Fish ◽

Brain Aromatase ◽

Circulating Levels ◽

Receptor Mrnas

Abstract Nucleobindin (Nucb)-1 and Nucb2 are DNA and Ca2+ binding proteins with multiple functions in vertebrates. Prohormone convertase-mediated processing of Nucb2 results in the production of biologically active nesfatin-1. Nesfatin-1 is involved in the regulation of reproduction in many vertebrates, including fish. Our lab originally reported a nesfatin-1-like peptide (Nlp) encoded in Nucb1 that exhibits nesfatin-1-like metabolic effects. We hypothesized that Nlp has a suppressive role in the reproductive physiology of fish. In this research, whether Nlp regulates reproductive hormones and oocyte maturation in fish were determined. Single intraperitoneal (IP) injection of goldfish Nlp (50 ng/g body weight) suppressed salmon and chicken gonadotropin-releasing hormone (sgnrh and cgnrh2), gonadotropin-inhibiting hormone (gnih) and its receptor (gnihr), and kisspeptin and brain aromatase mRNA expression in the hypothalamus of both male and female goldfish. In the pituitary, Nlp decreased mRNAs encoding lhb, fshb and kisspeptin and its receptor, while a significant increase in gnih and gnihr was observed. In the gonads, lh (only in male fish) and fsh receptor mRNAs were also significantly downregulated in Nlp-injected fish. Sex-specific modulation of gnih, gnihr, and kisspeptin system in the gonads was also observed. Nlp decreased sex steroidogenic enzyme encoding mRNAs and circulating levels of testosterone and estradiol. In addition, incubation of zebrafish ovarian follicles with Nlp resulted in a reduction in oocyte maturation. These results provide evidence for a robust role for Nlp in regulating reproductive hormones in goldfish and oocyte maturation in zebrafish, and these effects resemble that of nesfatin-1.

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Pharmacokinetics of Synthetic Human Parathyroid Hormone 1-34 in man Measured by Cytochemical Bioassay and Radioimmunoassay

Clinical Science ◽

10.1042/cs0680171 ◽

1985 ◽

Vol 68 (2) ◽

pp. 171-177 ◽

Cited By ~ 24

Author(s):

G. N. Kent ◽

N. Loveridge ◽

J. Reeve ◽

Joan M. Zanelli

Keyword(s):

Parathyroid Hormone ◽

Intravenous Injection ◽

Time Course ◽

Biologically Active ◽

Biological Degradation ◽

Human Parathyroid Hormone ◽

Subcutaneous Injections ◽

Cytochemical Bioassay ◽

Specific Radioimmunoassay ◽

Transit Times

1. Synthetic human parathyroid hormone (hPTH) 1-34 was given by intravenous injection to two healthy men. The time course of its appearance in and disappearance from the plasma was monitored both by cytochemical bioassay and by a specific radioimmunoassay (RIA) system. 2. Immunoreactive N-region parathyroid hormone (iPTH) reached peak concentrations in plasma at 2 min after injection, whereas peak concentrations of biologically active parathyroid hormone (bioPTH) were delayed until 4-6 min. Bioassayable PTH-like activity then disappeared from the plasma (mean transit times 5.8 and 8.6 min), approximately twice as fast as immuno-reactivity. 3. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems. 4. It was not possible to explain fully the non-parallel appearances of bio- and immuno-reactivities in the plasma after intravenous injection nor the non-parallel disappearances after both intravenous and subcutaneous injections on the basis of the present data. It seems likely, however, that in the process of biological degradation the immunoreactive locus is inactivated by a different reaction from that which destroys bioactivity. 5. To investigate these activity dissociations further will require the application of microfractionation procedures in conjunction with both types of assay system.

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Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin

Acta Endocrinologica ◽

10.1530/acta.0.1250127 ◽

1991 ◽

Vol 125 (2) ◽

pp. 127-131 ◽

Cited By ~ 6

Author(s):

Gorm Thamsborg ◽

Tommy L. Storm ◽

Henrik Daugaard ◽

Søren Schifter ◽

Ole H. Sørensen

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Nasal Spray ◽

Salmon Calcitonin ◽

Serum Levels ◽

Treated Group ◽

Human Calcitonin ◽

Vitamin D Metabolites ◽

Calciotropic Hormones ◽

Circulating Levels

Abstract. Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolitis.

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Parathyroid hormone degradation by opossum kidney cells via receptor-mediated endocytosis and lysosomal hydrolysis

Acta Endocrinologica ◽

10.1530/acta.0.1270267 ◽

1992 ◽

Vol 127 (3) ◽

pp. 267-270 ◽

Cited By ~ 5

Author(s):

Toru Yamaguchi ◽

Makoto Arao ◽

Masaaki Fukase

Keyword(s):

Parathyroid Hormone ◽

Biologically Active ◽

Main Role ◽

Kidney Cells ◽

Binding Studies ◽

Opossum Kidney ◽

Receptor Mediated Endocytosis ◽

Opossum Kidney Cell ◽

Opossum Kidney Cells

The mechanisms involved in parathyroid hormone (PTH) degradation by proximal renal tubule cells were studied using an opossum kidney cell line possessing PTH receptors as an in vitro model system. One hour incubation of 5 nmol/l human (h) PTH-(1-84) with intact opossum kidney cells (4.0× 106 cells) resulted in about 70% degradation and disappearance of hPTH-(1-84) from the medium, as determined by a two-site immunoradiometric assay. Preincubation with 100 nmol/l h[Nle8, Nle18, Tyr34]PTH-(1-34)amide for 6, 24, 48 and 72 h caused a 26, 47, 62 and 73% decrease, respectively, in PTH degradation by opossum kidney cells. Binding studies with 125I-labeled h[Nle8, Nle18, Tyr34]PTH-(1-34)amide as a radioligand showed that PTH receptor binding decreased with the time of pretreatment with the agonist. Pretreatments of the cells with monensin, an inhibitor of endocytosis, and the lysosomotropic agents such as chloroquine, ammonium chloride and leupeptin, inhibited degradation of hPTH-(1-84) by 87, 71, 76 and 72%, respectively. Concentrations of 5 nmol/l hPTH-(39-84) and hPTH-(39-68), which are known not to bind to PTH receptors appreciably, were not degraded by opossum kidney cells during 1 h incubations. Thus intact, biologically active PTH, but not its inactive fragments, is degraded by opossum kidney cells, by receptor-mediated endocytosis and lysosomal hydrolysis. A mechanism resembling the peritubular uptake of intact PTH by perfused kidneys reported previously appears to play a main role in PTH metabolism by cultured renal cells.

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Parathyroid hormone receptor in intact embryonic chicken bone: characterization and cellular localization.

The Journal of Cell Biology ◽

10.1083/jcb.94.2.379 ◽

1982 ◽

Vol 94 (2) ◽

pp. 379-386 ◽

Cited By ~ 137

Author(s):

C M Silve ◽

G T Hradek ◽

A L Jones ◽

C D Arnaud

Keyword(s):

Parathyroid Hormone ◽

Cellular Localization ◽

Adenosine Monophosphate ◽

Biologically Active ◽

Electron Microscopic Level ◽

Electron Microscopic ◽

Parathyroid Hormone Receptor ◽

Specific Localization ◽

Grain Distribution

The specific localization and the characterization of the parathyroid hormone (PTH) receptor in bone have been studied using 18-d embryonic chick calvariae and biologically active, electrolytically labeled [125I] bovine PTH(1-34). Binding was initiated by adding [125I]-bPTH(1-34) to bisected calvariae at 30 degrees C. Steady state binding was achieved at 90 min at which time 10 mg drg wt of calvaria specifically bound 17% of the added [125I]bPTH(1-34). Nonspecific binding in the presence of 244 nM unlabeled bPTH(1-34) was less than 2%. Insulin, glucagon, and calcitonin (1 microgram/ml) did not compete for PTH binding sites. Half-maximal inhibition of binding was achieved at concentrations of unlabeled bPTH(1-34) or bPTH(1-84) of about 10 nM. The range of concentration (2-100 nM) over which bPTH(1-34) and bPTH(1-84) stimulated cyclic 3'5'adenosine monophosphate (cAMP) production was similar to that which inhibited the binding of [125I]bPTH(1-34). Light microscope autoradiograms showed that grains were concentrated over cells (osteoblasts and progenitor cells) at the external surface of the calvariae and in trabeculae. In the presence of excess unlabeled PTH, labeling of control autoradiograms was reduced to near background levels. No labeling of osteocytes or osteoclasts was observed. At the electron microscopic level, grains were localized primarily over cell membranes. A quantitative analysis of grain distribution suggested that cellular internalization of PTH occurred.

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