Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “parathyroid hormone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed1984

Hypercalcemia associated with immunoreactive parathyroid hormone in a malignant rhabdoid tumor of the kidney (rhabdoid Wilms' tumor).

Severe hypercalcemia occurred in a child with metastatic disease from a rhabdoid tumor of the kidney. Because there was no evidence of skeletal involvement by tumor, an investigation of the cause for hypercalcemia was undertaken. A greatly elevated serum concentration of immunoreactive parathyroid hormone (iPTH) was documented. This together with the observation of histologically normal parathyroid glands and the immunohistologic demonstration of parathyroid hormone within tumor cells supports the hypothesis of ectopic iPTH production by the tumor. The concurrence of an unusual metabolic complication with an infrequently encountered tumor variant is notable.

Hormones, Ectopic↗
PubMed1996

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes.

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2-terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell.

Animals↗
PubMed1987

The canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification.

Covalent labeling of the canine renal parathyroid hormone receptor with [125I]bPTH(1-34) reveals several major binding components that display characteristics consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a beta 1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 [or 58,000 if the mass of bPTH(1-34) is excluded]. The binding of [125I]bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.

Animals↗
PubMed1994

Effect of parathyroid hormone and calcitonin on acetylcholine release in rat sympathetic superior cervical ganglion.

The effects of parathyroid hormone (PTH) and calcitonin on acetylcholine release by rat superior cervical ganglion (SCG) were evaluated in vitro. SCG labeled with [3H]choline were exposed to four 5 min-long pulses of 40 mM K+, 35 min apart. PTH increased, and calcitonin inhibited, in a dose-dependent way, K(+)-elicited [3H]acetylcholine release, with apparent effective doses 50 of about 10(-9) M. The effect of PTH was inhibited by co-incubation with the PTH receptor antagonist NLe [8-18]-PTH (3-34) amide. Incubation of SCG for 120 min with PTH or calcitonin resulted in dose-dependent augmentation or inhibition of K(+)-induced increase of high affinity [3H]choline uptake, respectively, with a maximal effect at 10(-8) M concentration (PTH) and 10(-9) M concentration (calcitonin) and declining at higher concentrations. The increase in SCG [3H]choline uptake induced by PTH was blunted by preincubation with the PTH antagonist NLe [8-18]-PTH (3-34) amide. At 10(-7) M concentrations, PTH increased significantly the in vitro conversion of [3H]choline to [3H]acetylcholine, an effect inhibited by PTH receptor antagonist. Calcitonin did not modify SCG [3H]acetylcholine synthesis by rat SCG. The results indicate that, in vitro, PTH increases, and calcitonin inhibits, acetylcholine release in rat SCG.

Acetylcholine↗
PubMed1976

Renal handling of phosphate in relation to serum parathyroid hormone levels.

The relation between the renal handling of phosphate, expressed as the maximal tubular reabsorption of phosphate (TmP)/glomerular filtration rate (GFR) index, and the serum concentration of immunoreactive parathyroid hormone (i-PTH) has been ivestigated in 15 patients with a very wide range of GFR, TmP/GFR and i-PTH. Seven patients had well functioning kidney allografts, with GFR ranging from 43.1 to 64.9 ml/min, while eight had varying degrees of chronic nephropathy, with GFR ranging from 26.7 to 2.3 ml/min. The TmP, the i-PTH concentration, the 51Cr EDTA clearance, the extracellular volume and the serum concentrations of calcium and standard bicarbonate were estimated during conditions where tubular reabsorption of phosphate was maximal. An inverse significant correlation was demonstrated between TmP/GFR and i-PTH (p less than 0.001), while none of the other investigated factors correlated to the TmP/GFR index. It is therefore concluded that the parathyroid hormone has a key role in the regulation of the tubular handling of phosphate in patients with impaired renal function.

Adult↗
PubMed2003

Efficacy data on teriparatide (parathyroid hormone) in patients with postmenopausal osteoporosis.

Until recently, the only therapeutic agents available for postmenopausal osteoporosis acted by inhibiting bone resorption and decreased the fracture risk by no more than 50%. Teriparatide, the recombinant 1-34 fragment of human parathyroid hormone, is a bone formation enhancer that has recently been licensed for use in established postmenopausal osteoporosis. Intermittent parathyroid hormone administration preferentially stimulates bone formation. The resultant increase in bone mass and improvement in bone architecture translate into a large decrease in the fracture risk that constitutes a major advance in the treatment of postmenopausal osteoporosis. Further work is needed to define the role for teriparatide in the therapeutic strategy for postmenopausal osteoporosis and to determine whether this agent is best used alone or in synchronous or sequential combination with bone resorption inhibitors.

Bone Resorption↗
PubMed2002

New signaling pathway for parathyroid hormone and cyclic AMP action on extracellular-regulated kinase and cell proliferation in bone cells. Checkpoint of modulation by cyclic AMP.

cAMP signaling, activated by extracellular stimuli such as parathyroid hormone, has cell type-specific effects important for cellular proliferation and differentiation in bone cells. Recent evidence of a second enzyme target for cAMP suggests divergent effects on extracellular-regulated kinase (ERK) activity depending on Epac/Rap1/B-Raf signaling. We investigated the molecular mechanism of the dual functionality of cAMP on cell proliferation in clonal bone cell types. MC3T3-E1 and ATDC5, but not MG63, express a 95-kDa isoform of B-Raf. cAMP stimulated Ras-independent and Rap1-dependent ERK phosphorylation and cell proliferation in B-Raf-expressing cells, but inhibited growth in B-Raf-lacking cells. The mitogenic action of cAMP was blocked by the ERK pathway inhibitor PD98059. In B-Raf-transduced MG63 cells, cAMP stimulated ERK activation and cell proliferation. Thus, B-Raf is the dominant molecular switch that permits differential cAMP-dependent regulation of ERK with important implications for cell proliferation in bone cells. These findings might explain the dual functionality of parathyroid hormone on osteoblastic cell proliferation.

3T3 Cells↗
PubMed2001

Postoperative course of serum parathyroid hormone and calcium after surgery for primary hyperparathyroidism.

The aim of this study was to describe the course of parathyroid hormone (PTH) and serum calcium after surgery for primary hyperparathyroidism, and to evaluate the usefulness of daily measurement of these parameters. PTH and serum calcium were daily monitored during the early postoperative period in 45 patients where a parathyroid adenoma was removed. PTH showed a sharp drop to a very low level already on the first postoperative day, whereafter a rapid recovery began. Serum calcium decreased more slowly: on the average, the lowest calcium level was seen on the second day. A majority of the patients were temporarily hypocalcemic, apparently to various degrees. After two weeks 38 patients showed a normal calcemia, while six patients remained slightly hypocalcemic. It is concluded that after removal of a parathyroid adenoma an abrupt fall of PTH precedes the decrease of serum calcium. The first day's PTH level is a reliable indicator of the success of the intervention and it should be a major point in the postoperative biochemical follow-up. Repeated measurements of serum calcium are useful, in contrast with the daily dosage of PTH which can be omitted for economical reasons.

Adenoma↗
PubMed1974

Immunoreactive forms of circulating parathyroid hormone in primary and ectopic hyperparathyroidism.

The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients with primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to non-parathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p<0.001) small (mol wt<9,500) COOH-terminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52+/-0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70+/-1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH [1-84] was the same in both syndromes (ectopic hyperparathyroidism, 0.82+/-0.22 ng eq/ml; primary hyperparathyroidism, 0.73+/-0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r=0.908; primary hyperparathyroidism, r=0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH [1-84] (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079); (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.

Adenocarcinoma↗
PubMed1979

Plasma catecholamine and parathyroid hormone responses in cattle during treadmill exercise at simulated high altitude.

When steers were exposed to treadmill exercise at a simulated altitude of 3500 m, plasma concentrations of epinephrine and norepinephrine as well as of parathyroid hormone increased within minutes. Heart rate, erythrocyte number and plasma lactic acid level rose at the same time, whereas plasma free fatty acids showed a later increase. It is concluded, that the elevated parathyroid hormone levels were probably caused by sympathetic stimulation.

Altitude↗
PubMed1971

Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog.

To evaluate the effects of parathyroid hormone and cyclic adenosine monophosphate on proximal tubular sodium and phosphate reabsorption, micropuncture studies were performed on dogs that received a highly purified preparation of parathyroid hormone (PTH), dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP), 5'-AMP, and saline. PTH resulted in a 30-40% inhibition of sodium and phosphate reabsorption in the proximal tubule unassociated with a rise in either total kidney or single nephron glomerular filtration rate (GFR). The bulk of the phosphate rejected proximally was excreted in the final urine while sodium excretion rose minimally despite the marked proximal inhibition, consistent with the presence of reabsorptive sites in the distal nephron for sodium but not phosphate. The infusion of dibutyryl cyclic AMP either systemically or directly into the renal artery inhibited proximal sodium and phosphate reabsorption in the absence of changes in either total kidney or single nephron GFR, resembling the effects of PTH quantitatively and qualitatively. In contrast, another adenine nucleotide, 5'-AMP, did not inhibit the reabsorption of either sodium or phosphate. These observations support the thesis that renal effects of PTH are mediated via stimulation of renal cortical adenyl cyclase. The infusion of a moderate saline load, 25 ml/kg, also produced a similar inhibition of proximal tubular fractional sodium and phosphate reabsorption with a marked phosphaturia but only minimal natriuresis. Thus, changes in sodium and phosphate reabsorption occur in parallel in the proximal tubule when sodium reabsorption is inhibited either with volume expansion or with administration of "specific" phosphaturic agents such as PTH or cyclic AMP. These data are consistent with the thesis that phosphate reabsorption is dependent upon proximal tubular sodium reabsorption wherein the phosphaturic effect of PTH might be the result of a primary inhibition of proximal tubular sodium reabsorption mediated by adenyl cyclase stimulation.

Adenine Nucleotides↗
PubMed1996

Structurally diverse N-terminal peptides of parathyroid hormone (PTH) and PTH-related peptide (PTHRP) inhibit the Na+/H+ exchanger NHE3 isoform by binding to the PTH/PTHRP receptor type I and activating distinct signaling pathways.

N-terminal peptides of parathyroid hormone (PTH) and PTH-related peptide (PTHRP) elicit a wide variety of biological responses in target cells, including the inhibition of Na+/H+ exchanger NHE3 activity in renal cells. This response is believed to be mediated by ligand binding to a common receptor (i.e. PTH/PTHRP receptor type I) and activation of cAMP-dependent and/or Ca2+/phospholipid-dependent protein kinases (PKA and PKC, respectively). However, the mechanism of action of these N-terminal peptides is now unclear because of recent data reporting the existence of additional receptor isoforms. Therefore, to directly examine the ligand binding and signaling characteristics of the PTH/PTHRP receptor type I and its ability to elicit a biological response, cDNAs encoding the rat type I receptor and the rat NHE3 isoform were transfected into Chinese hamster ovary (AP-1) cells that lack endogenous expression of these proteins. Competition binding assays using [125I-Tyr36]PTHRP-(1-36)-NH2 radioligand indicated that several biologically active human N-terminal PTH and PTHRP fragments (PTH-(1-34), PTH-(3-34), PTH-(28-42), PTH-(28-48), and PTHRP-(1-34)) were capable of binding to the type I receptor. Both PTH-(1-34) and PTHRP-(1-34) stimulated adenylate cyclase and PKC activities in these cells, whereas PTH-(3-34), PTH-(28-42), and PTH-(28-48) selectively enhanced only PKC activity. PTHRP-(1-16), a biologically inert fragment, was incapable of binding to this receptor and influencing either the PKA or PKC pathway. Furthermore, all the analogues with the exception of PTHRP-(1-16) inhibited NHE3 activity. Inhibition of PKC by the potent antagonist chelerythrine chloride abolished the depression of NHE3 activity by PTH-(3-34), PTH-(28-42), and PTH-(28-48) but did not alleviate the effects of PTH-(1-34). Likewise, antagonism of PKA by H-89 was unable to prevent the inhibition caused by PTH-(1-34). However, inhibition of both PKA and PKC by the nonselective protein kinase antagonist H-7 abolished the reduction of NHE3 activity by PTH-(1-34). These data indicate that discrete N-terminal analogues of PTH and PTHRP can interact with the classical PTH/PTHRP receptor type I and activate PKA and/or PKC. Activation of either signaling pathway independently leads to inhibition of NHE3.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Direct involvement of cAMP-dependent protein kinase in the regulation of alkaline phosphatase activity by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic UMR-106 cells.

The present study was performed to characterize the participation of parathyroid hormone (PTH)- and PTH-related peptide (PTHrP)-responsive dual signal transduction systems [cAMP-dependent protein kinase (PKA) and Calcium/protein kinase C (Ca/PKC)] in the regulation of alkaline phosphatase (ALP) activity in osteoblastic osteosarcoma cells (UMR-106). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M stimulated ALP activity to the similar degree. Dibutyryl, cAMP (dbcAMP) (10(-5), 10(-4) M) and Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), a direct stimulator of PKA (10(-4) M) also stimulated its activity. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, (10(-7), 10(-6) M) did not affect its activity, while calcium ionophores, A23187 and ionomycin (10(-7), 10(-6) M) inhibited it. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a direct inhibitor of PKA, (10(-4) M) did not affect ALP activity by itself, it significantly antagonized not only Sp-cAMPS-induced increase in ALP activity, but also PTH- and PTHrP-induced one. The present study first indicated that the activation of PKA was directly involved and acted as a main pathway in the regulation of ALP activity by PTH and PTHrP in osteoblasts.

Alkaline Phosphatase↗
PubMed1984

Intestinal absorption of calcium in greyhounds: the response to intermittent and continuous administration of human synthetic parathyroid hormone fragment 1-34 (hPTH 1-34).

Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.

Animals↗
PubMed2003

Parathyroid hormone venous sampling prior to reoperation for primary hyperparathyroidism.

BACKGROUND: The surgical cure rate for primary hyperparathyroidismis greater than 95%. For those who have recurrent or persistent disease, preoperative localization improves reoperation success rates. Selective parathyroid venous sampling (SPVS) for intact parathyroid hormone is particularly useful when non-invasive localization techniques are negative or inconclusive. METHODS: We present all known cases (n = 13)between 1994 and 2002 who had venous sampling for localization a tour institution prior to reoperation for recurrent or persistent primary hyperparathyroidism. Comparison was made with non-invasive localization procedures. Results of invasive and non-invasive localization were correlated with surgical findings. RESULTS: Of the nine reoperated cases, eight had positive correlations between SPVS and operative findings and histopathology. SPVS did not reveal the parathyroid hormone source in one case with negative non-invasive localization procedures. Comparisons between SPVS,computerized tomography (CT), and parathyroid scintigraphy (MIBI)as expressed in terms of true positive (TP), false positive (FP)and false negative (FN) were: SPVS - TP88.8%, FP 0%, FN 11.1%; CT - TP22.2%, FP 22.2%, FN 55.5%; and MIBI - TP33.3%, FP 0%, FN 66.6%. At least seven of the nine operated cases have been cured; another remained normocalcaemic 2 weeks after subtotal parathyroidectomy. CONCLUSION: In our institution SPVS has proven to be a valuable tool in cases with recurrent or persistent primary hyperparathyroidism and negative non-invasive localization procedures.

Adult↗
PubMed1975

New aspects of radioimmunochemical measurement of human parathyroid hormone using the labelled antibody technique.

Two forms of heterogeneity of parathyroid hormone (PTH) have given rise to conflicting results: one due to the heterogeneity of the secreted species from the gland and their peripheral metabolism and the other representing the immunochemical heterogeneity of the available antibodies. We have developed sequence specific assays using the technique of labelled antibodies. Therefore, results of assays measuring the C-terminal part and the (1-34)-N-terminal part of the molecule could be compared to those of an assay for hormone bearing both N- and C-terminal antigenic determinants. This assay is supposed to detect predominantly (1-84)-intact hormone. The immunoradiometric assay of (1-34)-PTH has a sensitivity of 0.04 ng/ml. This technique avoids the critical iodination of the hormone fragment containing no tyrosine. There is the expected overlap between normal subjects and patients with primary and secondary hyperparathyroidism. The most important finding are results from patients undergoing neck catheterization. We demonstrated nonuniform secretion of different species of PTH by parathyroid adenomata and normal glands. This supports the hypothesis of cleavage of the (1-84)-molecule in the gland.

Antigen-Antibody Reactions↗
PubMed1995

Truncation of the carboxyl-terminal region of the rat parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of adenylyl cyclase but not phospholipase C.

The functional role of the rat parathyroid hormone(PTH)/PTH-related peptide (PTHrP) receptor's carboxyl-terminal region was characterized by comparing the binding and signaling properties of receptors that have 78 and 111 amino acid deletions (R513 and R480, respectively), with those of the 591-amino acid wild-type (WT) receptor. R480 and R513 have 4- and 1.5-fold lower apparent Kd values for rat PTH-(1-34) (rPTH), compared with the WT receptor (WT, 1.81 +/- 0.19 nM; R513, 1.24 +/- 0.12 nM; R480, 0.48 +/- 0.05 nM, mean +/- S.E.). PTH (100 nM)-stimulated cAMP accumulation and polyphosphoinositide hydrolysis both correlated positively with receptor expression. However, whereas PTH-stimulated polyphosphoinositide hydrolysis was indistinguishable among WT and either truncated mutant at comparable levels of expressed receptors, maximal PTH-stimulated cAMP accumulation was 4-6- and 2-3-fold higher in cells expressing R480 and R513, respectively. Furthermore, pretreatment of COS-7 cells with 100 ng/ml of pertussis toxin (PTX) enhanced PTH-stimulated cAMP accumulation in cells expressing the WT receptor, but failed to do so in cells expressing either R480 or R513. Thus, sequences in the PTH/PTHrP receptor's carboxyl-terminal tail lower the affinity of the WT receptor for agonist; directly interact with, or indirectly facilitate the interaction of the receptor with a PTX-sensitive G protein that inhibits adenylyl cyclase; and decrease the efficacy with which the receptor interacts with Gs.

Adenylate Cyclase Toxin↗
PubMed1987

Effects of vitamin D3, 25-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion.

The active vitamin D metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] causes marked suppression of both pre-proparathyroid hormone messenger RNA (pre-proPTH mRNA) and parathyroid hormone (PTH) secretion. These effects are dose dependent and reversible when tested in an in vitro primary tissue culture cell system using normal bovine parathyroid cells. In the current studies, the precursors of 1,25(OH)2D3 and the related metabolite 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], were used in the same culture system to test for possible regulatory effects. The results were compared with identically prepared cells exposed to 1,25(OH)2D3. In short-term studies (30-120 minutes), none of the vitamin D-related compounds produced any effect on PTH secretion. In long-term studies (24-48 hours, using primary tissue culture in the presence of test agents), neither vitamin D3 nor 25(OH)D3 affected PTH secretion or pre-proPTH mRNA over the concentration range 10(-11)-10(-7) M. On the other hand, 24,25(OH)2D3 produced significant suppression of both pre-proPTH mRNA (77% of control, P less than .01) and PTH secretion (75% of control, P less than .005) at 10(-7) M. By comparison, 10(-11) M 1,25(OH)2D3 produced levels of suppression (25-30%) of both pre-proPTH mRNA and PTH secretion comparable to 10(-7) M 24,25(OH)2D3, while even greater suppression (40-50%) occurred at 10(-9)-10(-7) M 1,25(OH)2D3. From these studies, we conclude that vitamin D3 and 25(OH)D3 do not have significant effects on PTH synthesis and secretion over the range of doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗