13 results on '"Rodan SB"'
Search Results
2. Maintenance of parathyroid hormone response in clonal rat osteosarcoma lines.
- Author
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Majeska RJ, Rodan SB, and Rodan GA
- Subjects
- Animals, Calcitonin pharmacology, Follicle Stimulating Hormone pharmacology, Isoproterenol pharmacology, Osteosarcoma enzymology, Sarcoma, Experimental enzymology, Thyrotropin pharmacology, Adenylyl Cyclases metabolism, Clone Cells, Parathyroid Hormone pharmacology
- Published
- 1978
- Full Text
- View/download PDF
3. The effect of dexamethasone on parathyroid hormone stimulation of adenylate cyclase in ROS 17/2.8 cells.
- Author
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Rodan SB, Fischer MK, Egan JJ, Epstein PM, and Rodan GA
- Subjects
- 3',5'-Cyclic-AMP Phosphodiesterases metabolism, Animals, Cell Line, Colforsin, Corticosterone pharmacology, Cyclic AMP metabolism, Diterpenes pharmacology, Dose-Response Relationship, Drug, Guanylyl Imidodiphosphate pharmacology, Hydrocortisone pharmacology, Isoproterenol pharmacology, Mice, Time Factors, Adenylyl Cyclases metabolism, Dexamethasone pharmacology, Osteosarcoma enzymology, Parathyroid Hormone pharmacology
- Abstract
Treatment of ROS 17/2.8 osteosarcoma-derived cells with dexamethasone potentiates the PTH stimulation of adenylate cyclase in these cells, yielding a detectable response to as little as 10 pM PTH. Isoproterenol stimulation was also enhanced. The dexamethasone effect is first apparent at 12 h and increases with time of treatment. The apparent EC50 for dexamethasone is 3 nM. Hydrocortisone and corticosterone act similarly to dexamethasone, but require 30-fold higher concentrations. Dexamethasone treatment produces no change in high affinity phosphodiesterase activity. Glucocorticoid-potentiating effects are much more pronounced in whole cells than in broken cells and do not influence forskolin stimulation. Particulate fractions of dexamethasone-treated cells have higher adenylate cyclase specific activity, but are stimulated by guanyl-5'-yl imidodiphosphate to the same extent as control cells. These findings suggest that the glucocorticoids potentiate hormone responsiveness through promotion of hormone receptor-adenylate cyclase coupling by a mechanism dependent on cellular integrity.
- Published
- 1984
- Full Text
- View/download PDF
4. The role of Mg2+ in hormone stimulation of rat osteosarcoma adenylate cyclase.
- Author
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Rodan SB and Rodan GA
- Subjects
- Animals, Cattle, Cell Line, Dose-Response Relationship, Drug, Kinetics, Rats, Adenylyl Cyclases metabolism, Guanosine Triphosphate analogs & derivatives, Guanylyl Imidodiphosphate pharmacology, Isoproterenol pharmacology, Magnesium pharmacology, Osteosarcoma enzymology, Parathyroid Hormone pharmacology
- Abstract
1. Mg2+ concentration dependence of adenylate cyclase activity, in a rat osteosarcoma cell line (ROS 2/3), exhibits two apparent affinities with Km values of approx. 2 mM and 10 mM. 2. Only one Mg2+ affinity with a Km value of around 1 mM was apparent at saturating concentrations of: (i) guanosine-5'-(beta, gamma-imido)triphosphate; (ii) parathyroid hormone and GTP; and (iii) (-)-isoproterenol and GTP. 3. Conversely, at saturating concentrations of Mg2+ (40 mM) only high hormone concentrations, acting on low affinity sites, stimulated adenylate cyclase. 4. At saturating concentrations of guanosine-5'-(beta, gamma-imido)triphosphate, hormone stimulation decreased with increasing Mg2+ concentrations and none was seen at 40 mM Mg2+. The findings suggest that hormone stimulation of adenylate cyclase is associated with Mg2+ activation of a 'high hormone affinity' responsive state dependent on triphosphoguanine nucleotide. The hormone effect on Mg2+ affinity fully accounts for hormone stimulation of adenylate cyclase at physiologically relevant concentrations.
- Published
- 1981
5. Comparison of postreceptor effects of 1-34 human hypercalcemia factor and 1-34 human parathyroid hormone in rat osteosarcoma cells.
- Author
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Rodan SB, Noda M, Wesolowski G, Rosenblatt M, and Rodan GA
- Subjects
- Animals, Cell Division drug effects, Cell Line, Cyclic AMP metabolism, Dose-Response Relationship, Drug, Humans, Osteosarcoma metabolism, Osteosarcoma pathology, Parathyroid Hormone-Related Protein, Rats, Receptors, Cell Surface physiology, Receptors, Parathyroid Hormone, Sarcoma, Experimental pathology, Teriparatide, Hypercalcemia metabolism, Neoplasm Proteins pharmacology, Parathyroid Hormone pharmacology, Peptide Fragments pharmacology, Receptors, Cell Surface drug effects, Sarcoma, Experimental metabolism
- Abstract
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.
- Published
- 1988
- Full Text
- View/download PDF
6. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro.
- Author
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Horiuchi N, Caulfield MP, Fisher JE, Goldman ME, McKee RL, Reagan JE, Levy JJ, Nutt RF, Rodan SB, and Schofield TL
- Subjects
- Amino Acid Sequence, Animals, Calcium blood, Humans, Hypercalcemia etiology, Parathyroid Glands physiology, Parathyroid Hormone pharmacology, Rats, Rats, Inbred Strains, Thyroidectomy, Neoplasms physiopathology, Parathyroid Hormone physiology, Peptides physiology
- Abstract
One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.
- Published
- 1987
- Full Text
- View/download PDF
7. Evidence for preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum.
- Author
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Peck WA, Burks JK, Wilkins J, Rodan SB, and Rodan GA
- Subjects
- Animals, Bone and Bones drug effects, Cells, Cultured, Cyclic AMP metabolism, Peptide Fragments pharmacology, Periosteum drug effects, Rats, Adenosine pharmacology, Bone and Bones metabolism, Calcitonin pharmacology, Parathyroid Hormone pharmacology, Periosteum metabolism
- Abstract
In order to explore the distribution of hormone-responsive cells in skeletal tissues, we have examined the effects of synthetic bovine parathyroid hormone N-terminal peptide (bPTH 1-34) and salmon calcitonin (sCT) on cyclic AMP levels in periosteum-free rat calvaria, segments of periosteum, and in isolated cells dispersed from each tissue by collagenase digestion. Synthetic bovine PTH increased cyclic AMP levels to a greater degree in calvaria and in isolated bone cells than in the periosteal segments and cells, whereas sCT was more effective in the periosteal than in the bone systems. Primary cultures prepared from bone and periosteal cell populations exhibited progressive increases in their responsiveness to bPTH (1-34) and progressive decreases in responsiveness to sCT. After six days in the culture, bone cells failed to respond to sCT, and sCT did not modify their response simultaneously added bPTH (1-34). Six-day periosteal cell cultures exhibited residual sCT responsivity and an additive response upon simultaneous exposure to high concentrations of bPTH (1-34) and sCT suggesting separate sites of hormone action. Adenosine, a known stimulator of bone cell adenylyl cyclase, caused a greater increase in periosteal cell than in bone cell cyclic AMP. bPTH (1-34)-responsive cells which enrich periosteum-free bone may be osteoblasts, in view of their histological prominence in this tissue and in the bone cell isolates. Periosteal cells which responded to sCT and to adenosine preferentially are unidentified. Although periosteal segments contained numerous fibroblast-like cells, skin fibroblasts cultured from the same fetuses were sCT-insensitive. Growth in primary culture appears to alter the number of hormone-responsive cells or responsiveness of existing cells to each hormone, or both.
- Published
- 1977
- Full Text
- View/download PDF
8. Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats.
- Author
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Rodan GA, Rodan SB, and Marks SC Jr
- Subjects
- Adenylyl Cyclases metabolism, Adrenocorticotropic Hormone pharmacology, Animals, Calcitonin pharmacology, Dose-Response Relationship, Drug, Guanine Nucleotides pharmacology, Kidney enzymology, Rats, Skull, Bone and Bones metabolism, Lactates metabolism, Osteopetrosis metabolism, Parathyroid Hormone pharmacology
- Abstract
We have examined the effect of parathyroid hormone (PTH) on the adenylate cyclase activity of newborn osteopetrotic rat calvaria, to study a possible molecular basis for the reduced response of this mutant to PTH. Phenotypically normal littermates served as controls. We also measured the effect of PTH on kidney adenylate cyclase activity and on lactic acid accumulation in short term cultures of calvaria. PTH stimulated calvarial adenylate cyclase activity in a dose-dependent manner in both mutant rats and normal littermates. Lactic acid production was also enhanced by PTH, and no significant difference between mutants and normal littermates was observed. These findings indicate that the reduced response of the young osteopetrotic rats to PTH is not due to an absence of PTH receptors coupled to adenylate cyclase.
- Published
- 1978
- Full Text
- View/download PDF
9. Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factor.
- Author
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Rodan SB, Wesolowski G, Ianacone J, Thiede MA, and Rodan GA
- Subjects
- Adenylyl Cyclases metabolism, Cell Line, Humans, Parathyroid Hormone-Related Protein, RNA, Messenger analysis, RNA, Messenger drug effects, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured metabolism, Epidermal Growth Factor pharmacology, Neoplasm Proteins metabolism, Osteosarcoma metabolism, Parathyroid Hormone, Tetradecanoylphorbol Acetate pharmacology
- Abstract
A clonal cell line (Saos-2/B-10) derived from human osteosarcoma Saos-2 cells had the same osteoblastic characteristics as the mother line, but lacked sensitivity to parathyroid hormone (PTH) at early passages. At later passages (greater than 70) the cells became very sensitive to PTH (0.1 nmol/l). The absence of PTH-stimulatable adenylate cyclase correlated with the secretion of an adenylate cyclase-stimulatory activity which had the properties of the recently characterized PTH-like peptide (PTH-LP). This activity was inhibited by the PTH antagonist [8norleucyl,18norleucyl,34tyrosinyl]bovine PTH-(3-34)amide and could be neutralized by an antiserum raised against the synthetic PTH-LP-(1-34). Hybridization with a human PTH-LP cDNA showed that these cells produce two PTH-LP mRNAs of approximately 1.5 and 1.8 kb. The production of PTH-LP was stimulated by 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 150 nmol/l) and epidermal growth factor (EGF; 10 ng/ml). The increased accumulation of PTH-LP in conditioned media in response to TPA was seen after 1 h and levelled off at 6 h. In contrast, EGF stimulation was lower at 3 and 6 h but continued for 24 h. Both agents increased PTH-LP mRNA levels in Saos-2/B-10 cells. A TPA analogue which does not stimulate protein kinase C had no effect on PTH-LP production. Cycloheximide blocked the stimulatory effect of both TPA and EGF and the TPA effect was blocked by actinomycin D, suggesting transcriptional control. The regulation of PTH-LP by these agents may offer clues regarding the association of this protein with malignancy.
- Published
- 1989
- Full Text
- View/download PDF
10. Parathyroid hormone-responsive clonal cell lines from rat osteosarcoma.
- Author
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Majeska RJ, Rodan SB, and Rodan GA
- Subjects
- 1-Carboxyglutamic Acid metabolism, Alkaline Phosphatase metabolism, Animals, Clone Cells cytology, Clone Cells drug effects, Neoplasm Transplantation, Osteocalcin, Osteosarcoma pathology, Protein Biosynthesis, Rats, Adenylyl Cyclases metabolism, Osteosarcoma metabolism, Parathyroid Hormone pharmacology, Sarcoma, Experimental metabolism
- Abstract
Several clonal cell lines from a transplantable rat osteosarcoma, selected on the basis of parathyroid hormone (PTH)-sensitive adenylate cyclase, were established in culture. Bovine PTH-(1-84) (0.1 microM) stimulation of adenylate cyclase varied among clones from 8-fold to none. The level of PTH response was a stable property of each clonal line that was retained through numerous passages in vitro (nearly 3 yr in the oldest clone). Highly PTH-responsive lines had a cuboidal-eliptoid morphology and differed from the nonresponsive lines, which had a more fibroblastic appearance. PTH responsiveness correlated with several properties, presumably associated with the osteoblastic phenotype: elevated alkaline phosphatase activity, synthesis of the gamma-carboxyglutamic acid-containing bone protein, and production of mineralized tumors in host rats. PTH (1.0 nM; 24 h) reduced the alkaline phosphatase activity by 40% when tested in a responsive clone. The acid phosphatase activity of the various cell lines was uniformly low. These osteosarcoma-derived cell lines which are stable in vitro thus seem to reflect the phenotypic heterogeneity observed in the tumor in situ. They could be useful in studies of phenotypic expression, PTH action, and a possible relationship between the two.
- Published
- 1980
- Full Text
- View/download PDF
11. Parathyroid hormone and isoproterenol stimulation of adenylate cyclase in rat osteosarcoma clonal cells. Hormone competition and site heterogeneity.
- Author
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Rodan SB and Rodan GA
- Subjects
- Animals, Binding Sites drug effects, Binding, Competitive, Cattle, Cell Line, Dose-Response Relationship, Drug, Guanylyl Imidodiphosphate pharmacology, Rats, Receptors, Adrenergic, beta metabolism, Adenylyl Cyclases metabolism, Isoproterenol pharmacology, Osteosarcoma enzymology, Parathyroid Hormone pharmacology
- Abstract
A clonal cell line from rat osteosarcoma was found to possess parathyroid hormone and isoproterenol sensitive adenylate cyclase. This study examines the relationship between the two hormones and triphosphoguanine nucleotide with respect to enzyme activation. Concentration-dependence curves, analyzed by computer-aided curve fitting, revealed: (1) in the presence of 5 microM GTP there were two apparent affinities for parathyroid hormone (Km 9 and 89 nM) and isoproterenol (Km 72 and 340 nM; (2) and two affinities for guanosine-5' (beta, gamma-imido)triphosphate (Km 0.25 and 1.3 microM); (3) hormones and guanine nucleotides reciprocally shifted each other's concentration dependence curve to the high affinity sites; (4) parathyroid hormone and isoproterenol interacting with high affinity sites competed for the same adenylate cyclase; (5) parathyroid hormone and isoproterenol, acting on low affinity sites had additive effects and also stimulated adenylate cyclase in the absence of added guanine nucleotides. The findings are consistent with (i) competition of parathyroid hormone and isoproterenol for the activation of the high (hormone) affinity complex containing: receptors, nucleotide subunit, triphosphoguanine nucleotide, catalytic unit (ii) the apparent presence of receptor-nucleotide sub-unit GDP-catalytic unit complexes with low hormone affinity which are stimulated by parathyroid hormone and isoproterenol separately.
- Published
- 1981
12. The effect of parathyroid hormone and thyrocalcitonin on the accumulation of cyclic adenosine 3':5'-monophosphate in freshly isolated bone cells.
- Author
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Rodan SB and Rodan GA
- Subjects
- Adenylyl Cyclases metabolism, Animals, Bone and Bones cytology, Bone and Bones drug effects, Bone and Bones embryology, Bone and Bones enzymology, Cattle, Drug Synergism, Epinephrine pharmacology, Female, Hyaluronoglucosaminidase, Microbial Collagenase, Parathyroid Hormone administration & dosage, Pregnancy, Radioimmunoassay, Rats, Skull, Swine, Bone and Bones metabolism, Calcitonin pharmacology, Cyclic AMP metabolism, Parathyroid Hormone pharmacology
- Published
- 1974
13. Glucocorticoid treatment facilitates cyclic adenosine 3',5'-monophosphate-dependent protein kinase response in parathyroid hormone-responsive osteogenic sarcoma cells.
- Author
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Zajac JD, Livesey SA, Michelangeli VP, Rodan SB, Rodan GA, and Martin TJ
- Subjects
- Adenylyl Cyclases metabolism, Animals, Cell Line, Colforsin pharmacology, Cyclic AMP metabolism, Dexamethasone pharmacology, Enzyme Activation drug effects, Hydrocortisone pharmacology, Rats, Cyclic AMP pharmacology, Glucocorticoids pharmacology, Isoenzymes metabolism, Osteosarcoma metabolism, Parathyroid Hormone pharmacology, Protein Kinases metabolism
- Abstract
Late passage cultures of a clonal osteogenic sarcoma line (ROS 17/2.8) failed to respond to PTH with activation of cAMP-dependent protein kinase isoenzymes despite showing a sensitive and dose-dependent increase in cAMP after treatment with the hormone. When cells were treated with hydrocortisone or dexamethasone, protein kinase responsiveness to PTH was readily demonstrated; such treatment also resulted in enhanced cAMP production. Forskolin preincubation resulted in a cAMP response to PTH of similar magnitude to that seen with hydrocortisone but no activation of cAMP-dependent protein kinase occurred. Thus, the effect of glucocorticoid cannot be explained merely by the increased amplitude and sensitivity of the cAMP response which developed with glucocorticoid treatment in these cells. The data indicate that cellular activation of cAMP-dependent protein kinase does not automatically follow cAMP generation and that information transfer can be restored by pharmacological means.
- Published
- 1986
- Full Text
- View/download PDF
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