• 제목/요약/키워드: Human parathyroid hormone

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Endoproteolytic Processing of Human Parathyroid Hormone in Saccharomyces cerevisiae Mutants Lacking Genes Encoding the Yap3, Mkc7, and Kex2 Endoproteases

  • Choi, Won-A.;Kang, Hyun-Ah;Chung, Bong-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제9권5호
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    • pp.679-682
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    • 1999
  • When the human parathyroid hormone (hPTH) is expressed as a secretory product in S. cerevisiae, most of the secreted hPTH is internally cleaved by endoproteolytic processing. To investigate whether the yeast endoproteases such as Kex2p, Yap3p, and Mkc7p are involved in the endoproteolytic processing of hPTH in S. cerevisiae, hPTH was expressed in S. cerevisiae mutants deficient in one or two of the following well-known endoproteases such as Kex2p, Mkc7p, and Yap3p. Among these mutants, the yap3-disrupted(yap3$\Delta$) and yap3/mkc7-disrupted (yap3Δmkc7$\Delta$) yeasts showed a significant reduction in the extent of hPTH proteolysis. In contrast, the mkc7-disrupted (mkc7$\Delta$) yeast did not reduce the proteolysis of hPTH as compared to the wild type. This suggests that Mkc7p is not involved in the endoproteolytic processing of hPTH. It was also found that the kex2-disrupted (kex2$\Delta$) mutant was not able to secrete a detectable amount of hPTH.

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재조합 부갑상선 흘몬의 일반약리작용 (General Pharmacological Properties of Recombinant Human Parathyroid Hormone)

  • 이은방;장혜옥;이향주;천선아
    • Biomolecules & Therapeutics
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    • 제6권2호
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    • pp.159-164
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    • 1998
  • General pharmacological properties of recombinant human parathyroid hormone (hPTH) were examined. The administration of hPTH (7, 35 and 175 lU/kg sc) in mice had no effects in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazol solution. hPTH (9 and 44 lU/kg, sc) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration, and it did not influence the responses produced by injection of acetylcholine or epinephrine. It showed no direct effect at 4.4$\times$10$_{-2}$IU/ml in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also showed no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence intestinal propulsion at the doses of 7,35 and 175 lU/kg sc in mice. This drug exhibited no effect on urinary excretion at the doses of 7 and 35 lU/kg sc in rats. However, at a dose of 175 lU/kg sc, it showed a decreased urination along with decreased excretion of potassium, sodium and chloride ion. These results indicate that hPTH does not exert any of serious pharmacological effects except the inhibition of urination at a highest dose used.

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파골세포배야에서 나타난 부갑상선호르몬의 설치류 및 조류 파골세포에 대한 촉진 효과 (Recombinant Human Parathyroid Hormone Related Peptide (1-34) Stimulates Osteoclastic Bone Resorption in Both Rodent and Avian Disagsresated Osteoclast Culture)

  • 양대석;김일찬남궁용이창호
    • 한국동물학회지
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    • 제37권2호
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    • pp.255-261
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    • 1994
  • Recombinant human pBrathyriod hormone related peptide (1-341 (rhPTHrP) has been known to stimulate bone resorption in intact bone tissue culture system. Osteoclast has been known as a primary responsible cell for bone resorption. To examine the effect of rhPTHrP on this cell, we employed disaggregated rat osteodast culture. As a result, we found that rhPTHrP sisnificBntly elevates both the number and total area of resorbed pits in this culture. On the other hand, the conflicting results between disagsregated rat osteoc13st culture and Ca2+-deficient hen osteoclast culture system have been a big obstacle for the progress of bone research. To verify the differences between rat 3nd chick osteoclast system, we performed the same experiment using chick embryonic osteoclast. Since the similar results were obtained from the disaggregated chick osteoclast culture, the discrepancy between chick and rat osteoclast culture study seemed to be due to the difference in culture method, rather due to the species-difference.

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Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases

  • Soo Young Choi;Dami Yoon;Kang-Min Kim;Sun-Jong Kim;Heon-Young Kim;Jin-Woo Kim;Jung-Hyun Park
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제50권2호
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    • pp.103-109
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    • 2024
  • Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat diet-induced obese mice

  • Tae Yeon Kim;Chan Yoon Park;Sung Nim Han
    • Journal of Nutrition and Health
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    • 제56권1호
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    • pp.1-11
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    • 2023
  • Purpose: Obesity is associated with alterations in vitamin D metabolism and elevation of parathyroid hormone (PTH). Increased PTH level in obesity is likely one of the factors contributing to the dysregulation of vitamin D metabolism. We investigated the effects of lowering the PTH level in high-fat diet-induced obese mice on vitamin D metabolism. Methods: Five-week-old male C57BL/6N mice were fed either with control (10% energy as fat) or high-fat (60% energy as fat) diets ad libitum for 12 weeks, and vehicle or cinacalcet HCl (30 ㎍/g body weight) was gavaged daily during the final week of the experiment. The following groups were studied: CON (control diet + vehicle), HFD (high-fat diet + vehicle), and HFD-CIN (high-fat diet + cinacalcet HCl). PTH, 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D (25[OH]D), calcium, and phosphate levels in circulation, and the expression of genes related to vitamin D metabolism in the liver and kidneys were determined. Results: Renal 1α-hydroxylase expression in the HFD group was higher than that in the CON group despite the lack of a difference in the PTH levels between the 2 groups. The plasma PTH level in the HFD-CIN group was 60% lower than that in the HFD group (p < 0.05). In parallel, the HFD-CIN group had lower adipose tissue amount (9% lower), renal 1α-hydroxylase expression (48% lower), and plasma 1,25(OH)2D concentration (38% lower) than the HFD group. Conclusion: Lowering the PTH levels in high-fat diet-induced obese mice recovered the expression of renal 1α-hydroxylase and might be associated with lower amounts of white adipose tissue.

Vitamin D Sufficiency: How Should it be Defined and what are its Functional Indicators?

  • Hollis Broce W.
    • Nutritional Sciences
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    • 제8권2호
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    • pp.111-117
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    • 2005
  • It has been more than three decades since the first assay assessing circulating 25 (OH)D in human subjects was performed That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25 (OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25 (OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400 IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25 (OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25 (OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of 25 (OH)D$\leq$30 ng/mL. In certain cases, such as pregnancy and lactation, significantly higher circulating 25 (OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

Vitamin D Sufficiency: How should it be defined and what are its functional indicators?

  • Hollis Bruce W.
    • 한국영양학회:학술대회논문집
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    • 한국영양학회 2004년도 추계학술대회
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    • pp.22-33
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    • 2004
  • It has been more than three decades since the first assay assessing circulating 25(OH)D in human subjects was performed. That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25(OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25(OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25(OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25(OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of $25(OH)D{\leq}30ng/mL$. In certain cases, such as pregnancy and lactation, significantly higher circulating 25(OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

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