We assessed the relationships between lumbar bone mineral density (BMD) in middle and old-aged women and dietary habits, especially in their youth (about 18-25 years) and physiologic factors (height, weight, menarche, menopause, etc.). The subjects were 90 women at age 45-87 [63.5±9.5 (mean±SD) years] who visited our outpatient clinic of osteoporosis. Of them, 83 women had already ceased menstruation. Quantitave computed tomography (QCT) was used for measurements of the BMD of the trabecular bone in the third lumber vertebra (L3 expressed in mg/cm³ of CaCO₃), where pronounced changes associated with osteoporosis occur early.
There were significant negative correlations between age or menarcheal age and BMD of L3. Significant positive correlations were found between height or weight at the present and L3, but there was no correlation between body mass index (BMI) and L3. Significant positive correlations were noted between the values subtracted height at the present from height in the youth and L3. There were no correlations between frequency of pregnancy and delivery or outdoor life hour and L3. High milk-consumers in their youth (milk-drinking≥5 days per week) had higher L3 than low milk-consumers (milk-drinking≤2 days per week), and women, who had ate small fish 3 days or more per week in their youth, showed significantly higher L3 than thoes who had 2 days or less per week. We concluded that there are negative correlations between age or menarcheal age and L3 and positive correlations between height or weight and L3, and that low intake of milk and small fish in the youth may influence BMD in later years, leading to osteoporosis.

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine