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PubMed1982

Bone resorption under the influence of parathyroid hormone in vitro.

Parathyroid-induced bone resorption in vitro was observed by phase contrast microscope, 16 mm time-lapse cinemicrograph, light- and electron microscope. These findings led us to the following conclusions. That is, the macrophages seem to be capable of resorbing the bone tissue, and perhaps they may degrade and digest the collagen fibers, while the osteoclasts may resorb the bone minerals. The osteoclasts are destined to extinction after about two to three weeks of life span.

Animals↗
PubMed1975

Radioimmunoassay specific for amino (N) and carboxyl (C) terminal portion of parathyroid hormone.

A radioimmunoassay specific for the amino (N) terminal portion of the parathyroid hormone (PTH) molecule (N-PTH radioimmunoassay) has been developed by iodinating synthetic 1-34bovine PTH (1-34bPTH) and using commercially available bPTH antiserum. A radioimmunoassay specific for the carboxyl (C) terminal (C-PTH radioimmunoassay) has been carried out by adding enough amount of 1-34bPTH to the PTH radioimmunoassay system. The data obtained from N- and C-PTH radioimmunoassay were compared with those obtained from the PTH radioimmunoassay. It was observed that plasma levels of N-PTH, indicating biologically active PTH, were only one 8th to 32th to those of PTH and those of C-PTH were almost equal to those of PTH. These data corresponded well with those reported previously by using the antiserum specific for each terminal of the PTH molecule from the other laboratory. The half life of plasma N-PTH and C-PTH determined following the removal of parathyroid adenoma was less than 10 min and about 45 min respectively. These data indicate that the N-PTH radioimmunoassay can be done by iodinating 1-34bPTH and using commercially available antiserum.

Adenoma↗
PubMed1983

Secondary hyperparathyroidism in patients on maintenance hemodialysis: study of the N and C-terminal parathyroid hormones.

In 34 dialysis patients without secondary hyperparathyroidism and 10 dialysis patients with secondary hyperparathyroidism, the concentration of parathyroid hormone, total calcium, ionized calcium, inorganic phosphate, total alkaline phosphatase and bone alkaline phosphatase in serum were determined. The following results were obtained: serum N and C-terminal parathyroid hormone levels, serum total and ionized calcium levels, and serum total and bone alkaline phosphatase levels in dialysis patients with secondary hyperparathyroidism were higher than the corresponding values in cases of negative secondary hyperparathyroidism. Serum phosphate levels in dialysis patients with and without secondary hyperparathyroidism did not differ. Serum bone alkaline phosphatase activities were well correlated with serum total alkaline phosphatase activities in patients on hemodialysis.

Adolescent↗
PubMed2000

Intraoperative parathyroid aspiration and parathyroid hormone assay as an alternative to frozen section for tissue identification.

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at -70 degrees C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.

Biopsy, Needle↗
PubMed1976

Simultaneous ectopic production of parathyroid hormone and calcitonin.

Two patients with cancer were evaluated in whom there was evidence for the simultaneous ectopic production of parathyroid hormone (PTH) and calcitonin (CT). One patient had a gastric carcinoid and the other had a pancreatic islet cell carcinoma. Abnormal concentrations of parathyroid hormone and calcitonin were demonstrated by radioimmunoassay in the peripheral blood of each patient and in the gastric tumor. In the pancreatic tumor, immunohistologic studies also demonstrated the presence of CT and PTH and suggested that each hormone was produced by different cells of the tumor. Plasma concentrations of the hormones responded to functional tests of secretion and to tumor chemotherapy. These studies demonstrate the simultaneous ectopic production of the two physiologically antagonistic hormones, PTH and CT, and confirm their value as diagnostic markers for several types of malignancies.

Adenoma, Islet Cell↗
PubMed1991

Low serum calcium and high parathyroid hormone levels in neonates fed 'humanized' cow's milk-based formula.

We previously suggested that "late" neonatal hypocalcemia is related to a low calcium-phosphorus ratio of current cow's milk-based formula compared with human milk. However, there are no longitudinal studies of ionized calcium and parathyroid hormone concentrations in neonates receiving formulas with varying Ca/P ratios. Sixty-nine term neonates were studied through 2 weeks of age, and formula-fed neonates were randomized at birth to receive formula with molar ratios of 0.9, 1.2, or 1.4. Serum phosphate concentrations on days 2 and 6 of age were higher, and ionized calcium levels lower on days 6 and 14, in formula-fed vs human milk-fed neonates. Serum intact parathyroid hormone level increased between days 2 and 6 in formula-fed neonates compared with a decrease in human milk-fed neonates. Serum parathyroid hormone level on day 6 correlated with phosphorus intake among formula-fed neonates. No differences were noted in serum mineral or hormone levels among formula-fed groups. We speculate that the lowering of serum ionized calcium concentrations in neonates fed a modern "humanized" cow's milk formula may be a factor in late neonatal hypocalcemia.

Analysis of Variance↗
PubMed1991

[The importance of intact parathyroid hormone determination in the evaluation of parathyroid gland function].

The study investigates the importance of determining the intact parathormone in the evaluation of parathyroid gland function in different conditions of change in their function and the alteration of parathormone metabolism: primary and secondary hyperparathyroidism, hypoparathyroidism and hyperthyroidism. The role and place of intact parathormone determination in routine diagnostic schemes of calcium homeostasis disorders was reviewed by the simultaneous determination of the indicators of calcium and bone metabolism and other calcium homeostasis hormone regulators, as well as the C- and N-terminal parathormone fragments and by establishing their mutual links with the values of the intact parathormone.

Humans↗
PubMed1998

Estrogen via the estrogen receptor blocks cAMP-mediated parathyroid hormone (PTH)-stimulated osteoclast formation.

Several lines of evidence indicate that estrogen inhibits parathyroid hormone (PTH)-induced bone resorption in vivo and in vitro. However, its precise mechanism remains unknown. The present study was performed to investigate whether osteoclast precursor cells possess the receptors for PTH/PTH-related protein (PTHrP) and/or estrogen and to clarify the mechanism by which estrogen affects PTH-induced osteoclast-like cell (Ocl) formation. The polymerase chain reaction (PCR) product corresponding in size to the mouse PTH/PTHrP receptor cDNA was detected in mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as in osteoblastic MC3T3-E1 cells. The nucleotide sequence of the PTH/PTHrP receptor PCR product of hemopoietic blast cells was found to be 95.4% identical to that of PTH/PTHrP receptor cDNA of rat osteoblastic ROS cells. The PCR product corresponding in size to the mouse estrogen receptor cDNA was detected in mouse hemopoietic blast cells supported by GM-CSF as well as in MC3T3-E1 cells. The nucleotide sequence of the estrogen receptor PCR product of hemopoietic blast cells was completely identical to that of mouse estrogen receptor cDNA. 17Beta-estradiol (17beta-E2) but not 17alpha-E2 dose dependently antagonized Ocl formation stimulated by human (h) PTH(1-34) at a minimal effective concentration of 10(-10) M in the hemopoietic blast cell culture. 17Beta-E2 also significantly inhibited Ocl formation stimulated by 10(-8) M hPTHrP(1-34), while it did not affect 1,25-dihydroxyvitamin D3-induced Ocl formation. However, 10(-8) M 17beta-E2 significantly inhibited Ocl formation stimulated by dibutyryladenosine cAMP (10(-4) M) and Sp-cAMPS (10(-4) M), an activator of cAMP-dependent protein kinase (PKA) as well as forskolin (10(-5) M). In contrast, 17beta-E2 did not affect Ocl formation by either phorbol myristate acetate (10(-7) M), an activator of protein kinase C (PKC), or A23187 (10(-7) M), a calcium ionophore. The pretreatment with 17beta-E2 significantly inhibited Ocl formation induced by the combined treatment with PTH and PKC inhibitors (H7 or staurosporine), while it did not affect Ocl formation stimulated by the combined treatment with PTH and Rp-cAMPS, a PKA inhibitor. The present data indicate that estrogen inhibits PTH-stimulated Ocl formation by directly acting on hemopoietic blast cells, possibly through blocking a PKA pathway but not a calcium/PKC pathway.

Animals↗
PubMed1987

Effects of dietary calcium and age on parathyroid hormone, calcitonin and serum and milk minerals in the periparturient dairy cow.

Ten pregnant heifers and 10 pregnant cows (three or more pregnancies) were assigned to groups of five and fed either the recommended (low) amount of calcium or excess (high) calcium in their diet for 4 wk before parturition to determine the influence of prepartum calcium intake and age on hormonal control of peripartum calcium homeostasis. After parturition all groups received a diet with calcium adequate for lactation. Jugular blood samples from 21, 14, 7, 6, 5, 4, 3, 2, and 1 d prepartum through 0, 1, 2, 3, 5, 7, 14 and 21 d postpartum were assayed for concentration of parathyroid hormone, calcitonin, calcium, magnesium and phosphorus. Heifers and cows receiving high calcium diets had higher calcium and lower parathyroid hormone in blood serum before parturition than animals receiving the low calcium diets. Cows, but not heifers, fed high calcium diets exhibited severe hypocalcemia at parturition, remained hypocalcemic for 3 d and had low serum calcitonin. Regardless of dietary group, concentrations of parathyroid hormone and magnesium in serum increased after the first week of lactation. Feed intake during lactation, corrected for metabolic body weight, was similar for both dietary treatments and ages. Milk production per kilogram metabolic body weight was highest during the first week of lactation for cows fed low calcium diets before parturition. There was no correlation between hypocalcemia and loss of calcium in colostrum or milk. Feeding low dietary calcium to cows in the prepartum period was effective in the prevention of severe hypocalcemia at parturition. In contrast, dietary treatment of heifers had no effect on serum calcium concentration at parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Comparison of postreceptor effects of 1-34 human hypercalcemia factor and 1-34 human parathyroid hormone in rat osteosarcoma cells.

A tumor-derived factor believed to cause hypercalcemia by acting on the parathyroid hormone (PTH) receptor was recently purified, cloned, and found to have NH2-terminal sequence homology with PTH. The 1-34 region of this protein was synthesized, evaluated for its postreceptor effects on the ROS 17/2.8 cell line, and its properties were compared to 1-34 PTH. Both 1-34 human humoral hypercalcemia factor (HCF) and 1-34 PTH stimulated adenylate cyclase with an effective concentration (EC)50 of approximately 1 nM. The extent of stimulation by both peptides was equally enhanced by dexamethasone. They both had a pronounced inhibitory effect on growth in the presence of dexamethasone, with an EC50 of approximately 0.1 nM, reduced alkaline phosphatase (AP) activity by approximately 70% in the absence of dexamethasone and by approximately 80% in the presence of dexamethasone with an EC50 of 0.03 nM, and when present at a concentration of 10 nM, reduced AP mRNA levels (estimated by Northern analysis) by approximately 80% in the presence or absence of dexamethasone. Thus, in addition to similar dose-response curves for adenylate cyclase stimulation, both HCF and PTH produced identical postreceptor effects in ROS 17/2.8 cells. These effects of HCF are probably mediated by the interaction of the tumor-derived factor with the PTH receptor.

Animals↗
PubMed1994

A parathyroid hormone antagonist stimulates epidermal proliferation and hair growth in mice.

The biologic action of parathyroid hormone (PTH)-related peptide (PTHrP) in normal skin was investigated in cultured human keratinocytes and in SKH-1 hairless mice. The results indicate that the PTHrP agonists human PTHrP-(1-34) and PTH(1-34) are potent inhibitors of epidermal cell proliferation. [Nle8,18,Tyr34]bovine PTH-(7-34)-amide, an antagonist of the PTH/PTHrP receptor, blocked the inhibitory effect of PTH-(1-34) in cultured keratinocytes. In the SKH-1 mice, PTH-(7-34) caused a 244% increase of [3H]thymidine incorporation into isolated epidermal DNA and 246% and 180% increases in the number and length of hair shafts, respectively. Thus, PTH and PTHrP may play an important role in the normal physiology of skin, and their agonists and antagonists have potentially wide therapeutic applications in the treatment of hyperproliferative skin disorders and aging skin and could also be effective in stimulating and maintaining hair growth.

Animals↗
PubMed1986

Actions of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP formation in chicken and rat osteoclasts.

The effects of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP production were studied in osteoclast-rich cultures derived from medullary bone of laying hens and from the long bones of newborn rats. Cyclic AMP was assayed biochemically in replicate cultures, and furthermore, changes in cytoplasmic fluorescence were sought by indirect immunofluorescence with rabbit anti-cyclic AMP and FITC-labelled goat anti-rabbit IgG. Treatment of rat osteoclasts with calcitonin increased cyclic AMP formation as measured biochemically, and this was confirmed by the immunofluorescence method. No such increase took place in chick osteoclasts. Prostaglandin E2 increased cyclic AMP production in both rat and chick osteoclasts as determined by both methods. Since the immunofluorescence method failed to detect a response to parathyroid hormone either in chick or rat osteoclasts, its variable biochemical effects were concluded to be due to actions on contaminating osteoblasts in the cultures. Thus it has been possible with a combined biochemical and immunocytochemical approach to define the cyclic AMP responses to the calcium-regulating hormones in rat and chick osteoclasts. The failure of calcitonin to increase cyclic AMP in chick osteoclasts identifies a need to investigate the nature of calcitonin action on avian osteoclasts, which may contribute to understanding of its actions on mammalian cells.

Animals↗
PubMed1973

Acute parathyroid hormone response to epinephrine in vivo.

The acute effects of epinephrine, norepinephrine, and isoproterenol on the plasma immunoreactive parathyroid hormone (iPTH) response were studied in 13 550-600 kg cows. Catecholamines were infused for 7.0 min. During epinephrine infusions at 0.08 mumol/min iPTH increased from 0.48+/-0.12 (mean+/-SE, ng/ml) to 1.09+/-0.18 ng/ml (P < 0.02). Small increases in plasma free fatty acids and glucose could be detected with 0.08 mumol/min epinephrine; the iPTH response to epinephrine was as sensitive as the free fatty acid and glucose responses and possibly of physiological importance. Plasma calcium (total and ionized) and magnesium did not change. The responses were more pronounced at 0.8 mumol/min epinephrine with a mean iPTH increase from 0.49+/-0.16 ng/ml to 1.74+/-0.35 ng/ml (P < 0.01). Small decreases in plasma calcium occurred at 0.8 mumol/min epinephrine, but the plasma magnesium remained unchanged. However, when the plasma calcium was lowered with ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA), a much more pronounced lowering of the plasma calcium was required to produce comparable increases of the plasma iPTH concentrations than when epinephrine was infused. It appears that epinephrine has a direct effect on the release of iPTH from the parathyroid glands. Simultaneous infusions of calcium and epinephrine suppressed the stimulation by epinephrine. This points towards a common mechanism of the regulation of parathyroid hormone secretion caused by decreases in the extracellular calcium concentration and/or alterations in the distribution of calcium within parathyroid cells following the administration of epinephrine. The iPTH response to epinephrine was suppressed in the presence of propranolol. Isoproterenol was less active in raising iPTH than epinephrine, and norepinephrine was the least active. The stimulation by isoproterenol and the suppression by propranolol suggest beta adrenergic receptor sites within the parathyroid glands.

Animals↗
PubMed1978

Sigmoidal relationship between parathyroid hormone secretion rate and plasma calcium concentration in calves.

Parathyroid hormone (PTH) secretion rate was measured in 16 anesthetized calves by using a technique involving radioimmunoassay of parathyroid venous blood which was collected during timed intervals and measured volumetrically. The calves ranged in age from 2-14 weeks. Plasma calcium concentration was altered by infusion of solutions of CaCl2 or disodium ethylenediamine tetracetate (Na2 EDTA) into the jugular vein. When plasma calcium concentrations exceeded 10.5 mg/100 ml, a basal, non-suppressible secretion rate of 0.3 ng/kg/min was maintained despite the induction of hypercalcemia. Slight changes in secretion rate were observed in response to changes of plasma calcium in the range between 9 and 10.5 mg/100 ml. Below 9 mg/100 ml, a small decrease in plasma calcium concentration evoked a pronounced increase in secretion rate. A maximal secretion rate of about 5.5 ng/kg/min was attained at a plasma calcium concentration of approximately 7.5 mg/100 ml and it was not increased by more severe hypocalcemia. These observations confirm the sigmoidal relationship between PTH secretion rate and plasma calcium concentration which was previously suggested by measurement of PTH concentration in peripheral plasma of hypocalcemic, parturient cows.

Animals↗
PubMed1991

Elevated levels of parathyroid hormone in essential hypertensive patients with increased erythrocyte potassium efflux.

Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously hypertensive rats. On the other hand, it has been reported that hyperparathyroidism induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential hypertension quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential hypertensives. The quinine-sensitive K+ efflux was similar for hypertensive patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten hypertensives exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of parathyroid hormone (P less than .05). In addition, a positive correlation was found between parathyroid hormone and quinine-sensitive K+ efflux in the above ten hypertensives (R = 0.85, P less than .001). These results suggest that an excess of parathyroid hormone may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential hypertensive patients.

Adult↗
PubMed1968

A study of urinary excretion of parathyroid hormone in man.

A procedure for bioassaying parathyroid hormone-like activity in human urine has been developed. 24-hr urine samples were concentrated with dry Sephadex G-25 and bioassayed in the young thyroparathyrocauterized mouse by the measurement of whole blood calcium. Recovery of biological activity and radioiodinated beef parathyroid hormone was over 80%. Normal subjects usually excreted less than 30 U (USP) of activity per day while 18 patients with proven primary hyperparathyroidism excreted a mean of 182 U/day (USP). The activity was not found in 7 patients with hypoparathyroidism or in 5 patients with carcinoma of the breast, but was present in 9 patients with uremia and in 5 with carcinoma of the lung and hypercalcemia.

Animals↗
PubMed2001

Antenatal magnesium sulphate exposure is associated with prolonged parathyroid hormone suppression in preterm neonates.

UNLABELLED: The effects of maternal magnesium sulphate treatment on neonatal mineral status and parathyroid hormone secretory response were studied in 8 exposed and 27 control preterm infants during the first 2 wk of life. Antenatal magnesium sulphate resulted in hypermagnesaemia during the first 3-7 d of life without affecting other serum mineral concentrations. CONCLUSION: Early hypermagnesaemia was associated with hypercalciuria during the first 3 d and parathyroid hormone suppression up to the age of 2 wk in the exposed infants.

Calcium↗
PubMed1980

Cellular and subcellular localization of 1,25-(OH)2-vitamin D3 in rat kidney: comparison with localization of parathyroid hormone and estradiol.

Results of thaw-mount autoradiographic studies of kidney obtained 1--3 hr after a single injection of 1,25-(OH)2-[3H]vitamin D3 to rats showed strong nuclear concentration of radioactivity in podocytes and cells of distal tubules, including the pars convoluta, macula densa, and pars recta. Intermediate nuclear concentration was found in cells of the thin limb of Henle's loops, whereas weak or no nuclear uptake was seen in cells of the proximal tubules. In contrast, after injection of 3H-labeled parathyroid hormone or [3H]estradiol, mainly cells of the proximal tubules were labeled; after 3H-labeled parathyroid hormone, apical cytoplasmic uptake of radioactivity was seen most strongly in the proximal part of the proximal tubules, whereas, after [3H]estradiol, weak nuclear concentration was seen in cells throughout the proximal tubules. The results are consistent with the concept that synthesis of 1,25-(OH)2-vitamin D3 occurs in the proximal tubules under stimulation of parathyroid hormone or estradiol (or other hormones) and that the major site of action of 1,25-(OH)2-vitamin D3 is in the distal tubules.

Animals↗