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PubMed1977

Minor influence of parathyroid hormone on fractional tubular reabsorption of phosphate in chronic renal failure.

In untreated patients with chronic renal failure and glomerular filtration rates (GFR) between 10 and 25 ml/min the decrease in fractional tubular reabsorption of phosphate was correlated to the degree of secondary hyperparathyroidism. This correlation was not found in patients with GFR below 10 ml/min. During treatment with 1alpha-hydroxycholecalciferol for 11 weeks: a) serum parathyroid hormone concentration decreased in all patients on average 60%, and was normal in 5 patients after treatment b) fractional tubular reabsorption of phosphate decreased significantly (on average 0.21) c) glomerular filtration rate decreased significantly (on average 27.5%). Since the reduction (or normalization) of serum parathyroid hormone concentration did not increase the fractional tubular reabsorption of phosphate, other (GFR-related) factors than parathyroid hormone play the major role for renal handling of phosphate in chronic renal failure when GFR is below 25 ml/min.

Biological Transport↗
PubMedDate not supplied

Parathyroid hormone metabolites in renal failure: bioactivity and clinical implications.

Non-(1-84) parathyroid hormones (PTHs) are large circulating carboxyl-terminal PTH (C-PTH) fragments with a partially preserved amino-terminal structure. They were discovered during high-performance liquid chromatography (HPLC) analysis of circulating PTH molecular forms detected by an intact PTH (I-PTH) assay. Like other C-PTH fragments, they accumulate in blood in renal failure and account for up to 50% of I-PTH. They are secreted by the parathyroid glands in humans, and are generated by the peripheral metabolism of hPTH(1-84) in rats. The exact structure of non-(1-84)PTH fragments is not known. To study the possible role of non-(1-84) in PTH biology, hPTH(7-84) has been used as a surrogate, being the only large C fragment available on the market. In anesthetized, thyroparathyroidectomized rats, hPTH(7-84) caused hypocalcemia beyond that induced by surgery. It also blocked the calcemic response to hPTH(1-84) or hPTH(1-34). Other smaller C-PTH fragments, such as hPTH(39-84) and hPTH(53-84), were synergistic to hPTH(7-84) effects. hPTH(7-84) did not bind to the PTH/PTHrP receptor, but only to the C-PTH receptor in ROS 17/2.8 clonal cells, and did not stimulate cyclic adenosine monophosphate (cAMP) production by the same cells, suggesting that its hypocalcemic action was mediated via a receptor different from the PTH/PTHrP receptor, and that the calcium concentration resulted from the sum of the positive effect of hPTH(1-84) on the PTH/PTHrP receptor and of the negative effect of hPTH(7-84) and of C-PTH fragments on the C-PTH receptor. These data will change our understanding of circulating calcium regulation, which must now be viewed as the end result of opposite actions on two PTH receptors. PTH immunoheterogeneity, a highly regulated phenomenon, contributes to this dual biological effect, generating an agonist for the two different receptors. Clinically these results could have some implications in our knowledge of the PTH resistance of renal failure, of renal osteodystrophy, and of certain aspects of the uremic syndrome.

Animals↗
PubMed2005

Parathyroid hormone as an anabolic therapy for women and men.

The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.

Anabolic Agents↗
PubMed1995

Oxidation of recombinant human parathyroid hormone: effect of oxidized position on the biological activity.

PURPOSE: To determine the oxidation products of recombinant human parathyroid hormone (rhPTH) treated with H2O2, the amino acid residue oxidized, and the biological activity of the oxidation products. METHODS: Oxidized residues were determined by CNBr cleavage, trypsin digestion and subsequent fast atom bombardment mass spectrometry. The biological activity of each oxidized rhPTH was examined in rat osteosarcoma cell adenylate cyclase assay. RESULTS: Three oxidized products were isolated, namely, Met at position 8 (Met8) sulfoxide, Met at position 18 (Met18) sulfoxide and both positions Met sulfoxide. It appears that the Met8 and Met18 oxidized forms are intermediates in the generation of the Met doubly oxidized form. All oxidized forms possessed reduced biological activity, more so for oxidation at Met8 than at Met18. CONCLUSIONS: The region around Met8 is important for the activity of the parathyroid hormone.

Chromatography, High Pressure Liquid↗
PubMed2003

Rapid parathyroid hormone analysis during venous localization.

OBJECTIVE: To determine the usefulness of the rapid parathyroid hormone (PTH) assay during venous localization for primary hyperparathyroidism (1 degrees HPTH). SUMMARY BACKGROUND DATA: Remedial exploration for persistent 1 degrees HPTH poses a significant challenge when noninvasive preoperative localization studies are negative. Based on experience with the intraoperative rapid PTH assay, this technique was extrapolated to the interventional radiology suite and generated near real-time data for the interventional radiologist employing on-site hormone analysis, with a 12-minute turnaround time from blood sampling to assay result. METHODS: Between November 1997 and July 2002, 446 patients with 1 degrees HPTH were referred for treatment. Of these, 56 (12.5%) represented remedial patients who had each undergone one or more previous cervical explorations. Noninvasive imaging studies were positive for or suggestive of localized disease in 49/56 (87.5%) of these patients, who therefore proceeded directly to surgical exploration. Seven patients with persistent 1 degrees HPTH and negative noninvasive studies underwent selective venous sampling employing a rapid PTH assay in the interventional suite. RESULTS: Venous localization demonstrated an apparent PTH gradient in six of the seven patients. In three, a subtle gradient demonstrated in near real-time prompted additional sampling, which confirmed an unequivocal hormone gradient. In an additional case, the absence of a gradient on initial sampling prompted further sampling, which was positive. All of the patients were explored, and in five of the six patients with a positive PTH gradient, a parathyroid adenoma (mean weight 636 +/- 196 mg) was resected from a location predicted by venous localization. In the sixth patient with a positive gradient, parathyroid tissue was not identified; however, there was a significant fall in the intraoperative PTH values, and immediate postoperative and follow-up laboratory data at 1 month are indicative of a cure. In the one patient with negative localization, abnormal parathyroid tissue could not be located during surgical exploration. CONCLUSIONS: The rapid PTH assay is a major adjunct for obtaining informative venous localization in patients with persistent 1 degrees HPTH. This information is extremely helpful to the surgeon in this challenging group of patients and resulted in a 100% cure rate when a venous gradient was demonstrated. The authors now employ this technique routinely in remedial patients with negative noninvasive imaging studies.

Adenoma↗
PubMed1991

Values of intact serum parathyroid hormone in different stages of renal insufficiency.

Intact serum parathyroid hormone (PTH) values were determined in 136 patients consulting the out-patient clinic for renal medicine and in 36 patients on maintenance hemodialysis in order to reveal the extent of parathyroid involvement in different stages of renal insufficiency. Elevated PTH values were found in 53 of the conservatively treated patients and in all but 4 of those on hemodialysis. Serum creatinine values and the duration of uremia correlated significantly to serum PTH, and multivariate analyses revealed that these variables were of dominating importance in determining the extent of PTH elevation. The negative relationship between PTH and plasma ionized calcium indicated maintained calcium regulation of hormone release from the parathyroid, although a relative secretory autonomy seemed to develop in parallel with the functional renal impairment. It is concluded that measurements of intact serum PTH values can demonstrate parathyroid hypersecretion in early renal insufficiency and constitutes a useful tool in the management of patients with renal disease.

Adolescent↗
PubMed1982

Serum calcium, parathyroid hormone, and urinary cyclic adenosine monophosphate after parathyroidectomy.

In specific cases of primary hyperparathyroidism (HPT), an intraoperative measure of parathyroid function might aid the surgeon. Ideally this would permit the surgeons to recognize that sufficient parathyroid tissue had been removed to cure the patient, but that viable glandular tissue remains. This study was designed to evaluate the efficacy of urinary cyclic adenosine monophosphate (cAMP) concentrations as such a determinant. We studied serum calcium and parathyroid hormone concentrations and urinary cAMP levels in 11 control patients undergoing thyroid and non-neck operations and in 22 persons undergoing parathyroidectomy for primary HPT. The serum calcium and parathyroid hormone concentrations were normal in control patients and elevated in each person with primary HPT. Changes of these parameters after successful parathyroidectomy took too long either to occur or to be measured to be clinically useful intraoperatively. Basal urinary cAMP concentrations were normal in 10 of 11 control patients and remained so during their operations. Elevations of basal urinary cAMP levels were found in 78% of those with primary HPT. At 30 minutes after removal of all abnormal parathyroid tissue, urinary cAMP levels remained high in 41% of those in whom it as elevated in the basal state. However, by 60 minutes all urinary cAMP values were normal or low. Plasma cAMP values were normal in three of four patients with primary HPT and did not change within 90 minutes after operation despite the performance of a successful parathyroidectomy. As expected, urinary cAMP levels returned to normal in each of these individuals. Intraoperative changes of urinary cAMP levels do reflect changes in parathyroid status. However, because of the delay of 40 to 60 minutes before urinary cAMP normalizes after parathyroidectomy and because of the sophisticated technology necessary for rapid determination of this cyclic nucleotide, its present clinical applicability is limited.

Calcium↗
PubMed1979

[Superselective parathyroid hormone determination--a reliable diagnosis of the location of endocrinological active parathyroid neoplasms].

The importance of superselective catheterization of the small jugular veins for PTH-radioimmunoassay is shown as an improvement of the preoperative localization technique. Since May 1976 in 20 patients the diagnosis of pHPT could be established. Our own experiences with the method of small vein sampling combined with the radioimmunoassay demonstrate that a reliable localization of overactive parathyroid tumours is possible.

Humans↗
PubMed2000

The effects of age and gender on parathyroid hormone dynamics.

BACKGROUND AND AIMS: Hyperparathyroidism is a risk factor for bone loss. An age-related increase in parathyroid hormone (PTH) level has been demonstrated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D deficiency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects. SUBJECTS AND METHODS: Twelve young women with mean age +/- SD of 26.4 +/- 1.6 years, 12 young men with mean age of 26.6 +/- 1.3 years, 12 older women with mean age of 68.6 +/- 1.3 years and 12 older men with mean age of 67.2 +/- 1.6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Cai) were characterized by maximal and minimal iPTH levels, the set-points (levels of Cai causing half-maximal suppression of iPTH), and the slopes of the curves at the set-points. RESULTS: Baseline serum Ca, Cai, 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels, as well as the set-points, slopes and minimal values of the sigmoidal curves relating Cai to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not significantly higher in the older age groups (P = 0.18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not significant (P = 0.29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were significantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels. CONCLUSIONS: In both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in integrated PTH secretory response to changes in serum calcium. No alterations in the Cai/iPTH set-point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain.

Adult↗
PubMed2002

Applicability of intraoperative parathyroid hormone assay during thyroidectomy.

OBJECTIVE: To evaluate the applicability of intraoperative parathyroid hormone (quick PTH) assay to monitor parathyroid function and to identify clinically significant hypocalcemia compared with postoperative serum calcium monitoring. SUMMARY BACKGROUND DATA: Close monitoring of serum calcium levels is a standard of care to identify post-thyroidectomy hypocalcemia due to parathyroid insufficiency. METHODS: Quick PTH assay was performed before and after thyroidectomy for 100 patients at risk of postoperative hypocalcemia and 20 control patients who underwent unilateral lobectomy. Postoperative serum calcium levels were closely monitored. RESULTS: Control patients had a normal but 38.9 +/- 5.9% (mean +/- SEM) decline in quick PTH after thyroidectomy. Eleven of 100 at-risk patients (11%) developed postoperative hypocalcemia. Hypocalcemic patients had significantly lower quick PTH values after thyroidectomy compared with that of normocalcemic patients. Serum calcium was significantly lower in hypocalcemic patients the morning after operation but not early after the operation (within 6 hours). A normal or less than 75% decline in quick PTH after thyroidectomy can accurately identify normocalcemic patients during surgery as compared to more than 24 hours by serum calcium monitoring. CONCLUSIONS: The quick PTH assay can monitor parathyroid function during thyroidectomy and identify patients at risk of clinically significant hypocalcemia much earlier than serum calcium monitoring. It may facilitate early discharge and the use of parathyroid autotransplantation during thyroidectomy.

Adult↗
PubMed1988

Stimulation of chick adrenal steroidogenesis by avian parathyroid hormone.

Dispersed chick adrenocortical cells were incubated with avian parathyroid hormone (aPTH) or ACTH. Accumulation of cyclic AMP (cAMP), activity of cAMP-dependent protein kinase and the secretion of corticosterone and aldosterone, in response to these hormones, were measured. Accumulation of cAMP and activity of cAMP-dependent protein kinase were stimulated by both aPTH and ACTH as well as by cholera toxin. Cyclic AMP production followed a similar time-course when stimulated by either peptide hormone. Stimulation of steroid hormone secretion was detectable after 20 min of incubation with ACTH, but only after 40 min with aPTH. The maximal steroid hormone secretion by adrenocortical cells was similar when induced by either peptide hormone. The aPTH concentrations needed for half-maximal response of corticosterone and aldosterone secretion were higher than those for ACTH (2.5- and 2-fold respectively), but still within the physiological range. The 11 beta-hydroxylase inhibitor metyrapone inhibited the secretion of both corticosterone and aldosterone when induced by either aPTH or ACTH. The results suggest that aPTH is almost as potent as ACTH in stimulating the secretion of corticosterone and aldosterone from chick adrenocortical cells and utilizes a cAMP-dependent pathway similar to that of ACTH.

Adrenal Cortex↗
PubMed1985

[Calcitonin, parathyroid hormones, calcium ion, cyclic 3,5-adenosine monophosphate (cAMP) and erythrocyte deformability].

Calcium ion is one of the factors which modulate erythrocyte deformability. It is known that calciotropic hormones such as calcitonin (CT) and parathyroid hormone (PTH) exert hypocalcemizing and hypercalcemizing effects, respectively. Their action is mediated, at the level of their target cells, through adenylcyclase activation with the production of cyclic 3,5-adenosinmonophosphate (cAMP). Modifications of transmembrane calcium fluxes have been described and were attributed to these hormones. Erythrocyte deformability has been evaluated by Dormandy method of red blood cell filtration in hypocalcemic patients affected by hypoparathyroidism, in patients with hypercalcemia due to malignancy or primary hyperparathyroidism and in normal age- and sex-matched subjects. Erythrocyte filtration values resulted to be significantly increased with respect to normal values in hypercalcemic patients and at the lower limits of normality in hypocalcemic subjects. Subsequently, acute studies were performed in normal volunteers in whom venous infusions of synthetic salmon calcitonin determined a significant reduction of erythrocyte filtration values, whereas venous infusions of the 1-34 synthetic human PTH fragment induced a significant increase in filtration values of red blood cells. An infusion of a cAMP analogue, dibutyryl-cAMP, determined a slight reduction of erythrocyte filtration values. The calciotropic hormones influence erythrocyte deformability through mechanisms that are yet to be clarified.

Adenylyl Cyclases↗
PubMed2001

Regions in rat and human parathyroid hormone (PTH) 2 receptors controlling receptor interaction with PTH and with antagonist ligands.

The parathyroid hormone (PTH) 2 receptor is potently activated by tuberoinfundibular peptide (TIP39). Rat and human PTH2 receptors differ considerably in their PTH responsiveness. PTH weakly stimulates cAMP accumulation via the rat receptor, and here we show it did not detectably increase intracellular calcium ([Ca2+]i) and bound with low affinity (450 nM). For the human PTH2 receptor PTH was a full agonist for increasing cAMP, a partial agonist for increasing [Ca2+]i, and bound with high affinity (18 nM). In addition, the antagonists PTH(7-34) and TIP(7-39) bound with 10- to 49-fold lower affinity to the rat receptor. We investigated the molecular basis of differential PTH and antagonist interaction with human and rat PTH2 receptors by using chimeric human/rat PTH2 receptors. PTH cAMP-signaling efficacy (Emax) was determined by extracellular loop (EL) 1 and a region including EL2 and EL3. The N-terminal domain determined PTH binding selectivity at the inactive receptor state. Multiple regions throughout the receptor are required for the PTH-PTH2 receptor complex to adopt a high-affinity active state: inserting the rat receptor's N-terminal domain, EL1 or EL2/3, into the human receptor increased PTH's EC50 and reciprocal exchanges did not reduce EC50. This suggests the global receptor conformation prevents the rat receptor from adopting a high-affinity state when in complex with PTH. N-terminal ligand truncation, producing the antagonists PTH(7-34) and TIP(7-39), altered ligand interaction with the membrane-embedded domain of the receptor, eliminating EL2/3 as a specificity determinant and lowering binding affinity. These insights should contribute to the development of a high-affinity PTH2 receptor antagonist, for investigating the receptor's physiological role.

Algorithms↗
PubMed2001

Regulation of the nuclear orphan receptor Nur77 in bone by parathyroid hormone.

Osteoblasts function under the control of several hormones and growth factors. Among them, parathyroid hormone (PTH) and steroid hormones have significant effects on bone metabolism. We show that PTH induced the expression of Nur77, a member of the NGFI-B subfamily of nuclear orphan receptors in bone. PTH rapidly and transiently induced Nur77 mRNA in primary mouse osteoblasts that peaked at 1 h and at 10 nM of hormone. Cycloheximide did not affect the induction of Nur77 mRNA, suggesting that protein synthesis is not required for the PTH effect. PTH also induced Nur77 mRNA in calvariae cultures. Finally Nur77 protein expression was induced in nuclear protein extracts of cells treated with PTH. NGFI-B nuclear receptors have been implicated in retinoic acid, vitamin D, and thyroid hormone signaling. We propose that induction of NGFI-B nuclear orphan receptors represents a potential cross-talk mechanism between PTH and steroid hormone signaling to regulate bone metabolism.

Animals↗
PubMed1989

The central part of parathyroid hormone stimulates thymidine incorporation of chondrocytes.

The stimulation of DNA synthesis in primary cell cultures of chicken chondrocytes by parathyroid hormone was studied by assaying [3H]thymidine incorporation into DNA. Optimal assay conditions were determined by varying cell age, plating density, and incubation time. Under these conditions DNA synthesis was significantly stimulated by parathyroid hormone (PTH) and some of its fragments: cells treated with human (h)PTH(1-84), bovine (b)PTH(1-34) and [Nle8,18,Tyr34]bPTH(3-34)amide and hPTH(13-34) displayed 2.6-fold enhanced [3H]thymidine incorporation in a dose-dependent manner. The fragment hPTH(28-48) led to a similar stimulation, whereas [Tyr43]hPTH(43-68) and [Tyr52,Asp76]hPTH(52-84) had no effect. Using a series of synthetic hPTH peptides covering the central region of the hormone molecule (residues 25-47), we could delimitate further this putative mitogenic functional domain to a core region between amino acid residues 30 and 34. The effect of PTH on [3H]thymidine incorporation could not be mimicked by forskolin, indicating that the corresponding signal is not mediated by cAMP. It is, however, inhibited by EGTA and cannot be provoked in the absence of calcium ions in the medium. Therefore, the results presented indicate a hitherto unidentified functional domain of PTH in the central part of the molecule which exerts its mitogenic effect on chondrocytes in a cAMP-independent manner but seems to involve calcium ions for signal transduction.

Amino Acid Sequence↗
PubMed1978

Parathyroid hormone clearance in man.

The role of the kidney, liver, and bone and/or muscle, in the metabolic clearance of parathyroid hormone (PTH), has been examined in man. Serum was obtained from the femoral artery and the renal, hepatic, and femoral veins of nine hyperparathyroid patients undergoing selective venous catheterization. The concentration of immunoreactive parathyroid hormone (IPTH) was measured in the samples by radioimmunoassay using an antiserum predominantly specific for the aminoterminal (N-terminal) portion of the PTH molecule. Gel filtration of hyperparathyroid sera demonstrated this antiserum to measure essentially only intact PTH. The mean arteriovenous (AV) difference measured across the liver was 44%; across the kidney, 34%; and across the leg, 16%. These arteriovenous differences were all statistically significant (p less than 0.005). A significant positive correlation was found between the AV difference in IPTH across the kidney and the serum calcium concentration (r = 0.50, p less than 0.05). These studies suggest that both the liver and the kidney play major roles in the clearance of PTH in man and indicate that PTH is cleared by bone and/or muscle as well. The correlation observed between the serum calcium concentrations and the AV differences in IPTH across the kidney suggest that the rate of clearance of PTH in man may be modulated by changes in the concentration of serum calcium.

Adult↗
PubMed2005

Increased parathyroid hormone and decreased calcitriol during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: We noted that age-related normal calcium doses in neonates on venoarterial extracorporeal membrane oxygenation result in hypercalcemia. To avoid hypercalcemia and its potential consequences these infants are given one-half the normal calcium dose. We studied the pathogenesis of hypercalcemia and hypomagnesemia by evaluating calcitriol, intact parathyroid hormone, and calcitonin status during extracorporeal membrane oxygenation. DESIGN AND SETTING: Prospective, observational study in the intensive care unit of a 225-bed tertiary care pediatric hospital. PATIENTS AND PARTICIPANTS: Twelve neonates under 7 days old with severe pulmonary disease requiring extracorporeal membrane oxygenation. MEASUREMENTS AND RESULTS: Blood was obtained for intact parathyroid hormone and calcitriol concentrations before cannulation, during (extracorporeal membrane oxygenation days 2, 4, and predecannulation in those on >6 days), and after decannulation on days 1 and 3. Calcitonin concentrations were measured before cannulation, during, and after decannulation in the last seven patients. Prior to cannulation parathyroid hormone was normal (1.4-5.7 pmol/l) and on day 2 increased to 7.8+/-8.4 pmol/l. Before cannulation calcitriol was 14.5+/-8.21 pmol/l (normal 41-143 pmol/l), and concentrations remained low until after decannulation. In three of the seven infants calcitonin concentrations (normal <73 ng/l) were above the upper limit of the assay (>1150 ng/l) prior to cannulation and during extracorporeal membrane oxygenation. CONCLUSIONS: Regulation of the vitamin D-endocrine system during neonatal venoarterial extracorporeal membrane oxygenation appears to be aberrant compared to normal vitamin D-endocrine system regulation. The pathogenesis of this abnormality remains unclear and requires further study.

Analysis of Variance↗
PubMed1995

[Parathyroid hormone related-protein and calcium homeostasis].

Recently, parathyroid hormone-related protein (PTHrP) was identified as one of the major causes of humoral hypercalcemia of malignancy in several species. The hormone probably has an important role in the physiology and pathophysiology of mammals and birds. Many endocrine, paracrine and autocrine functions are attributed to PTHrP. Parathormone shares the same receptor with PTHrP. This receptor was isolated in many tissues. PTHrP could be an important fetal growth factor. The influence of PTHrP on calcium homeostasis is presently the object of active research. PTHrP stimulates calcium transfer through the placenta and maintains a concentration gradient between the dam's blood and the fetus. The hormone is produced in large quantities in milk. However, its exact and principal function in lactation has not yet been determined. Among other effects, PTHrP might stimulate the secretion of calcium, phosphate and magnesium in milk and might foster the development of the mammary gland. A role of PTHrP in the pathogenesis of postparturient paresis in dairy cows has been hypothesized. Results of recent trials demonstrate that despite an important role in calcium homeostasis, PTHrP is not pivotal in the development of milk fever.

Amino Acid Sequence↗