Effects of Dioxin and Estrogen on Collagenase-3 in UMR 106-01 Osteosarcoma Cells
Autor: | Hobart W. Walling, Mary F. Ruh, Gerald J. Fiacco, John J. Jeffrey, Nicola C. Partridge, O. Y. Barmina |
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Rok vydání: | 2000 |
Předmět: |
endocrine system
medicine.medical_specialty Polychlorinated Dibenzodioxins medicine.drug_class Biophysics Parathyroid hormone Stimulation Biochemistry Downregulation and upregulation Internal medicine Matrix Metalloproteinase 13 Tumor Cells Cultured medicine Extracellular Animals Humans Secretion Collagenases RNA Messenger Receptors Immunologic Receptor Molecular Biology Osteosarcoma Osteoblasts Estradiol Chemistry Rats Endocrinology Parathyroid Hormone Estrogen Cell culture Female Low Density Lipoprotein Receptor-Related Protein-1 hormones hormone substitutes and hormone antagonists |
Zdroj: | Archives of Biochemistry and Biophysics. 382:182-188 |
ISSN: | 0003-9861 |
DOI: | 10.1006/abbi.2000.1992 |
Popis: | Since estrogen is important in preventing osteoporosis in postmenopausal women and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an estrogen antagonist in reproductive tissues, we investigated the effects of 17beta-estradiol (E2) and TCDD on collagenase-3 secretion using parathyroid hormone (PTH)-stimulated UMR 106-01 cells, a rat osteoblastic osteosarcoma cell line. Whereas E2 or TCDD had no effect on UMR cells in the absence of PTH, cells grown in the presence of 10(-7) M PTH, which induces a dramatic 30-fold increase in collagenase-3 secretion, surprisingly demonstrated a further stimulation of collagenase-3 secretion in the presence of TCDD or E2. However, the potentiating response was biphasic; i.e., at higher concentrations of E2 or TCDD, there was no enhancement of the PTH effect. PTH induces multiple effects on UMR cells, including inducing collagenase-3 mRNA transcription and regulating its extracellular abundance through a specific receptor and endocytosis. Thus, we investigated the ability of TCDD or E2 to stimulate the induction of collagenase-3 mRNA using Northern analysis. As previously reported, PTH dose dependently induced collagenase-3 mRNA after 4 h of treatment. There was little effect of TCDD or E2 on PTH-induced levels of collagenase-3 mRNA. These data could not account for the final effects on secreted collagenase-3. We postulated that low concentrations of E2 and TCDD may downregulate the collagenase-3 endocytotic two-step receptor-mediated process that includes the LDL-receptor-related protein to enhance the effects of PTH. However, this was not the case. Therefore, we conclude that low concentrations of TCDD and estrogen alter translation or secretion of PTH-stimulated collagenase-3. |
Databáze: | OpenAIRE |
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