Serum concentrations of calcitonin and parathormone in the cord blood of premature infants

Determinations of serum calcium (Ca), calcitonin (CT) and parathyroid hormone (PTH) were carried out in mixed cord blood of 23 preterm infants. Gestational age ranged between 25 and 37 weeks. 17 of theme were vaginally delivered while 6 were delivered by emergency Caesarean section. 4 neonates died because of respiratory distress syndrome. The serum was stored at -30 degrees C until the determinations. Serum Ca levels were determined by spectrophotometry while CT and PTH levels by RIA (Immuno Nuclear Co). In cord serum the mean (M +/- SE) Ca,CT and PTH concentrations of all neonates examined were respectively: 9,9 +/- 0,6 mg/dl; 176 +/- 44 pg/ml and 1100 +/- 446 pg/ml. Serum values of CT and PTH in preterm newborns delivered by emergency Caesarean section were significantly higher than in those neonates vaginally delivered (CT: 302 +/- 115 vs 94 +/- 9 pg/ml; p less than 0.005) (PTH:2655 +/- 1857 vs 466 +/- 59 pg/ml; p less than 0.05). No differences were observed between serum CT and PTH levels in preterm neonates of different gestational age. Both CT and PTH serum concentrations were higher in neonates who died. In conclusion, the preterm neonate is able to secrete both peptides and to maintain Ca homeostasis; the mode of delivery likely affects the CT and PTH secretion; unexplainable high CT and PTH serum levels were detected in poor outcome preterm infants.     

Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats

In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.     

Endocrine regulation of calcium and phosphate in rat eye lens and its significance in cataract formation

Parathyroid hormone (PTH), calcitonin (CT)and calciferol (Vit. D3) operate synchronously to maintain a balance between calcium and phosphate levels in serum. An aberration of specific steps in the homeostatic process results in hypo/hyper phosphatemia. These aberrations may eventually lead to several diseased states. PTH and Vit. D3 induced hypercalcemia can, however, be significantly inhibited by calcitonin (CT). These findings have been correlated with the levels of calcium and phosphate obtained from human senile cataractous lenses of cortical and nuclear types. The comparison of the results indicate that amongst these three hormones PTH is most vulnerable in leading towards conditions for possible cataract formation in rat lens.     

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.     

Interactions between sodium and calcium intake and blood pressure responses to norepinephrine and parathyroid hormone

The present study has examined the vascular responses to infusion of norepinephrine (NE) and parathyroid hormone (PTH 1-34) in animals subjected for a six month period to one of four dietary regimens. Some animals received normal calcium chow (1.0% Ca by weight) and drank water (subgroup A), others consumed the same chow, but water was replaced by 0.5% saline (subgroup B), a third group consumed chow which had 2.0% Ca content and also drank 0.5% saline (subgroup C) and a fourth group consumed the 2.0% Ca chow, but drank water (subgroup D). No differences were found in the pressor response to NE across subgroup A, B, and C, while pressor response to NE in subgroup D was markedly reduced. Depressor responses to PTH were not significantly different across any of the four groups. The ability of changes in calcium homeostasis to affect blood pressure responses to NE and PTH were evaluated in animals consuming reduced dietary calcium (0.1%) for two and four weeks and compared with animals on normal calcium intake (1.0%). This dietary treatment resulted in only mild effects on calcium balance; after four weeks no significant difference in plasma total calcium concentration was observed, but plasma PTH levels were increased in animals on the low Ca diet. No effects on the blood pressure response to NE or PTH infusion were observed after 2 weeks of dietary treatment. At four weeks, NE responses remained unchanged, while responses to PTH were blunted in animals on 0.1% Ca chow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of xylazine immobilization on biochemical and endocrine values in white-tailed deer

The effect of xylazine hydrochloride on biochemical and endocrine parameters in plasma was examined in adult white-tailed deer (Odocoileus virginianus (Zimmermann]. In the first experiment, seven animals were injected intramuscularly via a blowgun dart with 0.65 mg/kg xylazine (100 mg/ml) and were bled 10, 20, 30, and 60 min post-injection. In the second experiment, eight animals were manually restrained for the first blood sampling and then injected manually and bled as before. Plasma calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (AP) were measured spectrophotometrically. Plasma parathyroid hormone (PTH), calcitonin (CT), thyroxine (T4), triiodothyronine (T3), and cortisol were measured by radioimmunoassay. Plasma PTH, CT, T4, T3, and AP activity did not differ (P greater than 0.05) during the 1 hr period studied in either experiment. Plasma Ca and P decreased significantly (P less than 0.05) in the second experiment, whereas cortisol levels increased significantly (P less than 0.05) 10 min post-injection in both experiments. The results may have been due to a drug effect or a combined drug and stress effect. It is suggested that xylazine may be safely used as an anesthetic in measuring PTH, CT, T4 and T3, and plasma AP up to 60 min post-injection in deer. Caution should be taken in using xylazine as an anesthetic to study adrenocortical function.     

Plasma parathyroid hormone during acute volume expansion in the rat

Various studies have suggested the possibility that volume expansion may increase parathyroid hormone (PTH) secretion. PTH appears to have renal effects consistent with the actions of a natriuretic and diuretic and the possibility exists that PTH may play a physiological role in volume homeostasis. The present studies were designed to examine whether PTH levels in plasma from rats was influenced by acute volume expansion and whether such effects were independent of alterations in plasma ionized calcium concentration. Volume expansion with calcium-free bicarbonate Ringers (10% of body weight, IV) led to a drop in plasma ionized calcium from 1.08 to 0.92 mMol/l (p less than 0.01) while plasma PTH concentration was increased from 67.2 to 114.2 pMol/l. Volume expansion with bicarbonate Ringers solution (also 10% of body wt, IV) which contained 1.8 mM CaCl2 was not associated with any significant change in either plasma ionized calcium or plasma PTH concentration. However, measurements of blood packed cell volume (PCV) revealed that infusion resulted in a drop in PCV from 49.7 to 41.1% (p less than 0.01). This represents a dilution of plasma of approximately 42%. The absence of any drop in plasma PTH during isocalcemic volume expansion suggests an underlying stimulus to PTH secretion during volume expansion independent of plasma ionized calcium levels.     

Calcium metabolism in post-menopausal women

To investigate some parameters involved in postmenopausal calcium metabolism we have measured FSH, LH, estradiol (E2), parathyroid hormone (PTH) calcitonin (CT), 25-hydroxy-vitamin D3 (25-OH-D3), total calcium (CaT) and ionic calcium (Ca++) serum levels in 20 healthy postmenopausal women and 20 premenopausal women. The results reported show that the decrease of estradiol levels are associated with a significant decrease in 25-OH-D3 serum levels, possibly as result of a lower concentration of vitamin D binding protein, which is extremely sensitive to changes in oestrogen levels. The PTH levels were similar in both groups studied, which might be explained together with increased ionic calcium levels in postmenopausal women, by decreased parathyroid sensitivity to the blocking action of Ca++.     

Vitamin D status and its modulatory effect on interferon gamma and interleukin-10 production by peripheral blood mononuclear cells in culture

ObjectivesWe aimed to investigate the influence of vitamin D on the production of the pro-inflammatory cytokine, interferon gamma (IFN-γ), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in peripheral blood mononuclear cell (PBMC) cultures.MethodsThirty healthy subjects were investigated. Serum levels of calcium, 25(OH) D, and parathyroid hormone (PTH) were assessed. PBMCs were activated in-vitro by phytohemagglutinin (PHA) in the presence and absence of vitamin D3 and then levels of IFN-γ and IL-10 were determined in culture supernatant using enzyme immunoassay.ResultsSerum calcium levels were significantly lower in the vitamin D deficient group while serum PTH levels were significantly higher in the vitamin D deficient group. PTH levels were inversely correlated to both calcium and 25(OH) D levels. In culture, vitamin D inhibited IFN-γ production and increased IL-10 production by PBMCs. Serum vitamin D status had no influence on the amount of cytokine produced in culture.ConclusionsThis study demonstrates that vitamin D modulates IFN-γ and IL-10 production and provides a rationale for evaluating vitamin D as an immunomodulatory agent.     

Effect of parathyroid hormone on plasma renin activity in humans

The effect of PTH infusion on PRA was evaluated in 22 normotensive subjects. Intravenous infusion of PTH produced an increase in PRA in studied subjects. This increase in PRA was dose dependent from 1.505 +/- 0.226 to 2.500 +/- 0.346 nmol/l/hour after administration of 100 units of PTH and from 1.648 +/- 0.189 to 4.294 +/- 0.614 nmol/l/hour after 200 units of PTH and was markedly decreased by a beta blocking drug from 1.660 +/- 0.259 to 2.498 +/- 0.485 nmol/l/hour. These responses were observed without any significant changes in plasma calcium and blood pressure. From our results we can conclude that PTH increases PRA in normotensive controls. This effect is partly blocked by beta adrenergic blockers.     

Electrophysiological responses of osteoclasts to hormones

Electrophysiological measurements were carried out on osteoclasts in vitro. Such isolated osteoclasts are able to resorb bone in vitro and contract in response to calcitonin (CT). Our measurements show that individual osteoclasts respond to CT with a significant transient hyperpolarization of membrane potential. Application of parathyroid hormone (PTH) and dibutyryl cAMP produced a transient hyperpolarization in some osteoclasts. Measurements on an osteoblastlike line (ROS 17/2.8) showed a sustained hyperpolarizing response to CT, which is similar to but smaller than the hyperpolarizing response to PTH and dibutyryl cAMP in this and some other osteoblastlike lines. In contrast to osteoblastlike cells, the osteoclasts have no long term membrane potential response to CT, to PTH, or to dibutyryl cAMP. These results show that there are distinct differences between osteoclasts and osteoblasts in their ion transport responses to hormones.     

甲状旁腺高血压因子和甲状旁腺素对细胞钙通道的不同作用

1989年Lewanczuk等[1]报道在自发性高血压大鼠（spontaneouslyhvnertensiverat,SHR）的血浆中发现一种具有独特升压效应的高血压因子．通过激活平滑肌细胞膜钙通道,提高细胞内游离钙（[Ca2 ]）水平起作用．随之证明这种循环血中的高血压因子来源于甲状旁腺,故称“甲状旁腺高血压因子（Parathyroidhypertensivefactor,PHF）”[2]。我们经实验研究证明,当给SD（Sprague-Dawley）大鼠注射经透析的SHR血浆后30min其血压开始升高,45min达高峰,60min恢复到注射前水平．同时经透析的血浆可使SD大鼠尾动脉条的细胞45Ca2 摄取增加,其…     

Effects of age on plasma levels of calcium-regulating hormones and bone status in male SAMP8 mice

This study was undertaken to examine whether the plasma levels of calcium-regulating hormones and bone status alter with age in male senescence accelerated mice (SAM), SAMP8. Age-matched senescence-resistant mice, SAMR1, were used as controls. The blood and femur samples were collected at 2.5 months of age (M) and then monthly from 3 to 12 M for physicochemical analyses, biochemical analyses, and the determination of hormones by radioimmunoassay. With advancing age, the plasma calcitonin (CT) levels decreased progressively, and the plasma parathyroid hormone (PTH) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3) levels increased in both SAMR1 and SAMP8. The plasma calcium concentrations were maintained within a narrow range throughout the experimental period, while the plasma phosphorus (P) concentrations decreased with age in both strains. In contrast to SAMR1, the curves of age-related changes in the plasma CT levels and P concentrations were lower, and those in the plasma PTH levels were higher in SAMP8. The femoral bone densities and calcium contents increased gradually with age from the beginning of the experiment and peaked at 6 M in both strains, then declined. Those peaks were lower in SAMP8 than in SAMR1. These results indicate that the male SAMP8 develops osteoporotic signs earlier than SAMR1, and is proved to be a satisfactory animal model for longitudinal studies related to osteoporosis for men.     

钙敏感受体在骨代谢中的研究进展

钙敏感受体感受细胞外的钙离子水平,调控一系列激素的释放以维持机体的钙稳态。钙稳态的调节过程与骨代谢相偶联,钙敏感受体通过直接或间接对破骨和成骨细胞的调控,动员或者抑制骨钙入血。虽然钙敏感受体已被证实调控骨代谢,但是详尽的调控机制仍在不断探究中。目前认为细胞外的高钙水平会激活钙敏感受体,抑制甲状旁腺激素分泌并促进降钙素释放,进而破骨细胞被抑制,成骨细胞动员,增加了骨质合成。本文就近年来关于钙敏感受体调控骨代谢的研究进展作一综述,为促进钙敏感受体及相关作用因子治疗骨代谢疾病的研究提供参考。     

Pre-Transplantation Serum Parathyroid Hormone Influences the Number of Mobilized CD34+ Hematopoietic Stem Cells in Autologous Hematopoietic Stem Cell Transplantation

Background:Parathyroid hormone (PTH) is a calcium homeostasis regulator and can affect bone marrow niche. PTH leads to the bone marrow stem cell niche expansion as well as the induction of stem cell mobilization from the bone marrow into peripheral blood. In this study, we evaluated the association between pre- transplantation serum PTH levels and the number of circulating CD34+ cells along with the platelets/white blood cells (Plt/WBC) engraftment in patients who underwent autologous Hematopoietic Stem Cell Transplantation.Methods:Subjects for the study were 100 patients who received autologous hematopoietic stem cell transplantation (auto-HSCT), retrospectively. Serum levels of PTH, calcium, phosphorus, and alkaline phosphatase were measured before mobilization. Their impacts were measured on the number of mobilized CD34+ hematopoietic stem cells, and Plt/WBC engraftment.Results:High levels of serum PTH (> 63.10 pg/mL) was significantly associated with higher number of CD34+ cells in peripheral blood after granulocyte- colony stimulating factor (G-CSF)-induced mobilization (p= 0.079*). Serum calcium at low levels were associated with higher number of circulating CD34+ cells post mobilization. Pre- transplantation serum levels of phosphorus and alkaline phosphatase on CD34+ numbers were not statistically significant. Serum Plt/WBC engraftment was not improved in presence of high levels of serum PTH.Conclusion:We suggested that serum PTH levels before transplantation could be influential in raising the number of circulating CD34+ hematopoietic stem cell after mobilization.Key Words: Auto-HSCT, CD34+ Cell, Pre- transplant PTH     

Clinical use of calcimimetics in the treatment of hyperparathyroidisms

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in the extracellular ionized calcium concentration (Ca(2+)ec) regulates parathormone (PTH) and calcitonin secretion, urinary calcium excretion and ultimately bone turnover. Cloning of CaR and discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. CaR became an ideal target for the development of compounds able to modulate the activity of CaR, activators (calcimimetics) as well as inhibitors (calcilytics). The calcimimetics are able to amplify the sensitivity of the CaR to Ca(2+)ec, suppressing PTH levels with a resultant fall in blood Ca2+. They dose-dependently reduce the secretion of PTH in vitro in cultured parathyroid cells, in animal models and in humans. In uremic animals, these compounds prevent parathyroid cell hyperplasia, normalize plasma PTH levels and bone remodelling. In uremic patients undergoing hemodialysis, the calcimimetics reduce plasma PTH concentration at short-term (12 weeks) as well as at long-term (2 years), serum calcium-phosphorus product and bone remodelling. After one year of treatment, these patients show a gain of bone mass of 2-3% at the femoral neck and at the total body. Contrarily, the calcilytics, by inhibiting CaR, can intermittently stimulate the secretion and the serum concentration of PTH. This results in an skeletal anabolic effect with a substantial increase in bone mineral density. They are potentially very interesting for the treatment of post-menopausal osteoporosis.     

Norepinephrine interference in adrenal hormone balance related to blood calcium effects of PTH (author's transl)]

Decreased hypercalcemic effects of PTH are observed after medulloadrenalectomy, (table I), metoprione (table II) or cortisone (table IV) treatments in guinea pigs. 2. Norepinephrine restores the blood calcium effects of PTH in these cases but epinephrine is inactive. 3. Immediate activation of kidney adenylate cyclase by PTH (increased urinary AMPc) is also reduced in medulloadrenalectomised, cortisone or metopirone treated guinea pigs (table V). But in this test, norepinephrine reduces the effect of PTH (fig. 1).     

Hypocalcaemia and serum levels of inorganic phosphorus, magnesium parathyroid and calcitonin hormones in the last month of pregnancy in Awassi fat-tail ewes

Serum levels of calcium (Ca), inorganic phosphorus (P), magnesium (Mg), parathyroid (PTH) and calcitonin (CT) hormones of fat-tail Awassi ewes were determined during the last month of pregnancy. The incidence of hypocalcaemia (HCE) was 13.4% of the obstetrical cases examined. Twenty-six (81.3%) of 32 ewes with HCE were 4 yr of age or older. Significant decreases (p less than 0.01) in serum Ca levels from normal values or controls (n = 6; 10.04 +/- 0.22% (w/w)) to pathological values (4.30 +/- 0.35% (w/w)) caused severe clinical manifestations in 75% of affected ewes. This HCE was accompanied by a significant increase in the PTH level (142.6 +/- 9.1 pmol/l in comparison to 99.7 +/- 9.3 pmol/l in controls, p less than 0.05) and significant decrease in serum CT level (98.2 +/- 7.6 pg/ml in comparison to 144.6 +/- 25.7 pg/ml in controls; p less than 0.05). Intravenous administration of Ca borogluconate yielded normal Ca levels which were accompanied by a decrease in serum PTH levels and an increase in CT levels to normal values.     

Correlation between cyclic AMP levels and calcium efflux in isolated renal cortical tubules.

Isolated renal cortical tubules from male hamsters were utilized to examine the possible relationship between cyclic AMP (cAMP) and efflux of calcium. Both parathyroid hormone (PTH) and prostaglandin E1 (PGE1) produced dose-related increases in cAMP levels and calcium efflux from isolated tubules. Maximal concentrations of both hormones resulted in changes in cAMP which were 6 fold greater and changes in calcium efflux which were 2 fold greater with PGE1 than with PTH. Effects of sub-maximal amounts of either hormone on both cAMP and calcium efflux were potentiated to tubule incubations resulted in increases in tissue-associated cAMP over the same degree by inclusion of methyl-isobutylxanthine (MIX). Addition of either exogenous cAMP or dibutyryl cAMP (db-cAMP) produced dose-related increases in calcium efflux which occurred more rapidly with db-cAMP than with cAMP. Increasing amounts of cAMP added to the same concentration range resulting in increases in calcium efflux. Addition of 2', 3' cyclic AMP, 5'AMP or db-cyclic GMP had no significant effect on calcium efflux while 3', 5' cyclic CMP significantly reduced this response. The results indicate that cAMP increases efflux of calcium from renal tubules and may play a central role in hormone-dependent transport of this ion.