Increased rat femur osteocalcin mRNA concentrations following in vivo administration of thyroid hormone
Tóm tắt
Thyroid hormone has a direct resorptive effect on bone. Thyroid hormone therapy in doses that suppress pituitary TSH production result in a reduction in bone density. Osteocalcin is a bone matrix protein. Serum levels are a sensitive marker for bone turnover and are increased in hyperthyroid patients. In order to establish an animal model to study the effects of thyroid hormone on bone turnover, we measured rat femur osteocalcin mRNA following in vivo administration of thyroid hormone. Young CD rats weighing 60–90 g were given daily ip injections of T3, T4, or saline (control) for 12 days. Blood was obtained for radioimmunoassays, and RNA was extracted from femurs and analyzed by Northern blot using a 60-mer synthetic oligonucleotide probe corresponding to bases 360–420 of rat osteocalcin mRNA, labeled with [32P] ATP by 5′-endlabeling. Serum TSH concentrations were suppressed to subnormal levels by the lowest doses of T3 and T4, and to undetectable levels by the higher doses. Increases in serum T3 and T4 concentrations were proportional to the dose of each administered hormone. T3, 5 and 10 µg/100 g body weight, resulted in a 43% and 62% increase in osteocalcin mRNA, respectively. T4, 5, 10, and 20 µg/100 g body weight, resulted in a 35%, 47%, and 135% increase in osteocalcin mRNA, respectively. These data demonstrate that in vivo administration of either T4 or T3 to young rats results in a significant dose-dependent increase in femur osteocalcin mRNA concentrations.
Tài liệu tham khảo
Mundy G.R., Shapiro J.L., Bandelin J.C., Canalis E.M., Raisz L.G. Direct stimulation of bone resorption by thyroid hormones. J. Clin. Invest. 58: 529, 1976.
Auwerx J., Bouillon R. Mineral and bone metabolism in thyroid disease: A review. Quart. J. Med. 60: 737, 1986.
Epstein S. Serum and urinary markers of bone remodelling: Assessment of bone turnover. Endocr. Rev. 9: 437, 1988.
Garrel D.R., Delmas P.D., Malavai L., Tourniaare J. Serum bone Gla protein: A marker of bone turnover in hyperthyroidism. J. Clin. Endocrinol. Metab. 62: 1052, 1986.
Lukert B.P., Higgins J.C., Stoskopf M.M. Serum osteocalcin is increased in patients with hyperthyroidism and decreased in patients receiving glucocorticoids. J. Clin. Endocrinol. Metab. 62: 1056, 1986.
Martinez M.E., Herranz L., de Pedro C., Pallardo L.F. Osteocalcin levels in patients with hyper- and hypothyroidism. Horm. Metab. Res. 18: 212, 1986.
Johansen J.S., Thomsen K., Christiansen C. A radioimmunity for bone Gla protein (BGP) in human plasma. Acta Endocrinol. (Copenh.) 114: 410, 1987.
Lee M.S., Kim S.Y., Lee M.C., Cho B.Y., Lee H.K., Koh C-S., Min H.K. Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism. J. Clin. Endocrinol. Metab. 70: 766, 1990.
Faber J., Perrild H., Johansen J.S. Bone Gla protein and sex hormone-binding globulin in nontoxic goiter: Parameters for metabolic status at the tissue level. J. Clin. Endocrinol. Metab. 70: 49, 1990.
Ross D.S., Ardisson L.J., Nussbaum S.R., Meskell M.J. Serum osteocalcin in patients taking I-thyroxine who have subclinical hyperthyroidism. J. Clin. Endocrinol. Metab. 72: 507, 1991.
Kieffer J.D., Mover H., Federico P., Maloof F. Pituitary-thyroid axis in neonatal and adult rats: comparison of the sexes. Endocrinology 98: 295, 1976.
Gautvik K.M.-, Tashjian A.H., Kourides I.A., Weintraub B.D., Graeber C.T., Maloof F., Suzuki K., Zuckerman J.E. Thyrotropin-releasing hormone is not the sole physiologic mediator of prolactin release during suckling. N. Engl. J. Med. 290: 1162, 1974.
Ridgway E.C., Weintraub B.D., Cevallos J.L., Rack C., Maloof F. Suppression of pituitary TSH secretion in the patient with a hyperfunctioning thyroid nodule. J. Clin. Invest. 52: 2783, 1973.
Chirgwin J.M., Przybyla A.E., MacDonald R.J., Rutter W.J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294, 1979.
Thomas P.S. Hybridization of denaturated RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA 77: 5201, 1980.
Maxam A.M., Gilbert W. Sequence end-labeled DNA with base specific chemical cleavages. Methods Enzymol. 65: 499, 1980.
Duncan D.B. Multiple range and multiple tests. Biometrics 11: 1, 1985.
Ross D.S., Neer R.M., Ridgway E.C., Daniels G.H. Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thryoxine. Am. J. Med. 82: 1167, 1987.
Paul T.L., Kerrigan J., Kelly A.M., Braverman L.E., Baran D.T. Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women. JAMA 259: 3137, 1988.
Klaushofer K., Hoffman O., Gleispach H., Leis H-J., Czerwenka E., Koller K., Peterlik M. Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria. J. Bone Min. Res. 4: 305, 1989.
Soskolne W.A., Schwartz Z., Goldstein M., Ornoy A. The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone remodelling of mouse long bone in vitro. Bone 11: 301, 1990.
Rizzoli R., Poser J., Bürgi U. Nuclear thyroid hormone receptors in cultured bone cells. Metabolism 35: 71, 1986.
Sato K., Han D.C., Fujii Y., Tsushiba T., Shizume K. Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osetoblastic cells (ROS 17/2.8) through 3, 5, 3′-triiodo-L-thyronine nuclear receptors. Endocrinology 120: 1873, 1987.
LeBron B.A., Pekary A.E., Mirell C., Hahn T.J., Hershman J.M. Thyroid hormone 5′-deiodinase activity, nuclear binding, and effects on mitogenesis in UMR-106 osteoblastic osteosarcoma cells. J. Bone Min. Res. 4: 173, 1989.
Kasono K., Sato K., Han D.C., Fujii Y., Tsushima T., Shizume K. Stimulation of alkaline phosphatase activity by thyroid hormone in mouse osteoblast-like cells (MC3T3-E1): a possibile mechanism of hyper-alkaline phosphatasia in hyperthyroidism. Bone Min. 4: 355, 1988.
Kaplan M.M. The role of thyroid hormone deiodination in the regulation of hypothalamo-pituitary function. Neuroendocrinology 38: 254, 1984.
High W.B., Capen C.C., Black H.E. Effects of thyroxine on cortical bone remodelling in adult dogs. A histomorphometric study. Am. J. Pathol. 102: 438, 1981.
Demay M.B., Roth D.A., Kronenberg H.M. Regions of the rat osteocalcin gene which mediate the effect of 1,25-dihydroxyvitamin D3 on Gene transcription. J. Biol. Chem. 264: 2279, 1989.
Lian J., Stewart C., Puchacz E., Mackowiak S., Shalhoud V., Collart D., Zambetti G., Stein G. Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl. Acad. Sci USA 86: 1143, 1989.
Morrison N.A., Shine J., Fragonas J-C., Verkest V., McMenemy M.L., Eismam J.A. 1,25-dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. Science 246: 1158, 1989.
Bouillion R., Muls E., De Moor P. Influence of thyroid function on the serum concentration of 1,25-dihydroxyvitamin D3. J. Clin. Endocrinol. Metab. 51: 793, 1980.
Weisman Y., Eisenberg Z., Lubelski R., Spirer Z., Edelstein S., Harell A. Decreased 1,25-dihydroxycholecalciferol and increased 25-hydroxy- and 24, 25-dihydroxycholecalciferol in tissues of rats treated with thyroxine. Calcif. Tissue Int. 33: 445, 1981.
Kano K., Jones G. Direct in vitro effect of thyroid hormones on 25-hydroxyvitamin D3 metabolism in the perfused rat kidney. Endocrinology 114: 330, 1984.
Mackowiak S., Gerstenfeld L.C. Effect of thyroid hormone on osteocalcin synthesis. J. Bone Min. Res. 3: S172, 1988 (Abstract).