1990 Fiscal Year Final Research Report Summary
Enzymic Degradation of Parathyroid Hormone and Its Control
| Project/Area Number |
62440048
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
FUJITA Takuo Kobe University School of Medicine, Professor, 医学部, 教授 (30009964)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Toshitsugu Kobe University School of Medicine, Research Associate, 医学部, 助手 (00226458)
BABA Hisamitsu Kobe University, University Hospital, Research Associate, 医学部附属病院, 助手 (70189728)
FUKASE Masaski Kobe University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (80116243)
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| Project Period (FY) |
1987 – 1990
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| Keywords | Parathyroid Hormone(PTH) / Proteolytic Enzyme / Degradation / UMR-106 Cells / OK Cells / Kidney / Osteoblasts / C-Kinase |
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| Research Abstract |
Protein peptide hormones, after being synthesized, are degraded either before or after reaching the target organs and exerting their actions, producing various fragments. Such degradation and metabolics of hormone themselves are closely associated with their actions. In order to understand the mechanism of hormone action and their control, it is imperative to clarify the mechanism and significance of its degration. Heterogeneity of parathyroid hormone because of the presence of various fragments was demonstrated for the first time, followed by reports on similar phenomena as to other hormones. Degradation of parathyroid hormone has been studied for many years, but its enzymatic mechanism and relationship with the hormone action remains unknown.
In the initial stage of the present study, a unique neutral protease specifically cleaving parathyroid hormone was extracted and purified from the cytosolic fraction of rat renal cortex. Unlike cathepsins of lysosomal origin so far held responsib
… More
le for the specific hydrolysis of parathyroid hormone, this cytosolic neutral protease cleaves the 1-84 intact parathyroid hormone at two distinct sites, 34-35 and 35-70 and 71-84. Though the N-terminal fragment 1-34 is known to possess the full hormone activity, the significance of C-fragments so far remains unknown.
We have shown for the first time the dose dependent inhibition of dexamethasoneーstimulated alkaline phosphatase activity by C-terminal fragments of PTH in Ros 17/2.8 osteosarcoma cell line with osteoblastーlike activities.
In order to clarify the cellular origin of PHT-hydrolyzing enzymes, attempts were also made to test the PTH-hydrolyzing activity of opossom kidney cell line (OK cell) and osteoblast-like osteosarcoma cell line, UMR-106.
A chymotrypsin-like enzyme with a specific parathyroid hormone-hydrolyzing activity of was demonstrated in both of these cell lines. The activity of this enzyme was closely associated with PTH receptor and under the control of intracellular signal transduction system involving protein phosphorylation system such as A-and C-kinase. This may indicate a breakthrough to the elucidation of interrelationship between parathyroid hormone action and degradation. Less
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