Isamu Nagai

Binding of the carboxyl-terminal fragments of human parathyroid hormone to rat osteoblastic cells ROS 17/2.8

We have recently demonstrated that the carboxyl-terminal (C-terminal) PTH fragments increase or decrease alkaline phosphatase activity in dexamethasone-treated ROS 17/2.8 cells, depending on the length of deletion of amino-terminal amino acids of the PTH molecule, and interact with amino-terminal (N-terminal) PTH fragment [Acta Endocrinol 128:367]. In the present study, we examined individual and combined inhibitory effects of N-terminal and a series of truncated C-terminal PTH fragments [PTH (1-34), (35-84), (53-84) and (71-84)] on the binding of intact PTH molecule [PTH (1-84)] to ROS 17/2.8 cells.The C-terminal PTH fragments, as well as the N-terminal PTH fragment, partially inhibited the binding of [35S]-labeled PTH (1-84) to the cells. The inhibitory effect of C-terminal PTH fragments was reduced along with the deletion of aminoterminal amino acids of the PTH molecule, but still retained in the shortest C-terminal PTH fragment, PTH (71-84). When added together, PTH (1-34) reinforced the inhibitory effect of each C-terminal PTH fragment. The combination of PTH (1-34) and the complementary C-terminal PTH fragment, PTH (35-84), resulted in inhibition of [35S] PTH (1-84) binding to the level obtained by addition of the same concentration of unlabeled PTH (1-84).These findings suggested that the region relatively close to the C-terminal end of the PTH molecule might be essential for the binding of C-terminal PTH fragment could be responsible for the modification of the binding affinity of the peptide to the receptor and the action of the peptide.

The [53–63] amino acid portion of the parathyroid hormone molecule is essential for the stimulatory effect of carboxyl-terminal PTH fragments on alkaline phosphatase activity in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8

The effect of a series of truncated carboxyl-terminal parathyroid hormone (PTH) fragments on alkaline phosphatase (ALP) activity was further examined in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8. As we previously reported, dexamethasone-induced ALP activity was inhibited not only by hPTH(1-84) and aminoterminal PTH fragment hPTH(1-34), but also by carboxyl-terminal PTH fragment hPTH(69-84). The longer carboxyl-terminal PTH fragment hPTH(53-84) stimulated ALP activity, and the shorter carboxyl-terminal PTH fragment hPTH(71-84) did not affect ALP activity.The longest newly synthesized carboxyl-terminal PTH fragment hPTH(35-84), which is complementary to amino-terminal PTH fragment hPTH(1-34), stimulated ALP activity as potently as hPTH(53-84), but not more potently than hPTH(53-84). Another newly synthesized carboxyl-terminal PTH fragment hPTH(64-84), which has an intermediate peptide length between hPTH (53-84) and hPTH(69-84), inhibited ALP activity as potently as hPTH(69-84).These results suggest that the 35-52 amino acid portion of the PTH molecule might not be crucial for the stimulatory effect of carboxyl-terminal PTH fragments on ALP activity, and that the 53–63 portion, but not the 64–68 portion, of the PTH molecule might be essential for the stimulatory effect of carboxyl-terminal PTH fragments on ALP activity. Furthermore, the importance of the 69th and 70th amino acid of the PTH molecule for the inhibitory effect of carboxyl-terminal PTH fragments on ALP activity was confirmed.

Changing distribution of obesity index in freshmen students of Kobe University from 1975 to 1985

1. We determined changes of the mean levels of height, weight, BMI (body mass index) and blood pressure among Japanese freshmen students (n = 9708) of Kobe University for a period of 10 years (1975 to 1985). 2. We observed the distribution of obesity index calculated on Welfare Ministry’s standard body weight among Japanese freshmen students in 1975 and 1984. 3. We checked the body measurement and blood pressure of 1214 male students of Kobe University (1980); those who have no history of alcohol drinking, liver disease (except fatty liver) and glucosuria. 4. The blood samples were examined for SGGT, SGPT, cholinesterase (CHE), total cholesterol, triglyceride (TG), serum uric acid and fasting blood glucose. Fatty liver findings were observed using ultrasonographic method (TOSHIBA, SAL32B).