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. 1987 Sep;84(17):6267–6271. doi: 10.1073/pnas.84.17.6267

17 beta-estradiol acts directly on the clonal osteoblastic cell line UMR106.

T K Gray, T C Flynn, K M Gray, L M Nabell
PMCID: PMC299052  PMID: 2819869

Abstract

We studied the effect of 17 beta-estradiol (E) on the proliferation and alkaline phosphatase activity of cultured UMR106 cells, a clonal osteoblastic cell line. Growth rates were reduced and alkaline phosphatase activity was increased in cells incubated for 2 days in medium containing E (10(-8) M). In contrast, E had no effect on the growth rates or alkaline phosphatase of a human fibroblastic cell line, S90E. The effect of E was not observed with low cell density or at confluence. 1,25-Dihydroxyvitamin D3 antagonized the response to E. Preincubation of the cells with dexamethasone, a potent inducer of differentiation, reversed the effect of E or 1,25-dihydroxyvitamin D3. These results indicate that cellular and/or extracellular factors such as cell density, the phase of the cell cycle, the state of differentiation, and the presence or absence of other steroids influenced the response of UMR106 cells to E. Serum was removed from the culture medium to minimize the effect of the steroids, growth factors, and nutrients present in serum. A striking stimulation of alkaline phosphatase by E occurred with serum-free conditions. This stimulation was biphasic over an E concentration from 10(-12) to 10(-8) M, with the peak response at 10(-10) M. The action of E on UMR106 cells was metabolite-specific, since the isomer 17 alpha-estradiol produced no effect on proliferation rates or alkaline phosphatase activity. The cyclic AMP response to parathyroid hormone (residues 1-34) was not altered by E treatment of these cells. In contrast, dexamethasone exposure did increase the cyclic AMP response to parathyroid hormone. These results demonstrate a direct effect of E on an osteoblastic cell line. They also raise the possibility that similar or identical actions of E occur in cultured normal osteoblasts.

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Selected References

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  1. Burnett C. C., Reddi A. H. Influence of estrogen and progesterone on matrix-induced endochondral bone formation. Calcif Tissue Int. 1983 Jul;35(4-5):609–614. doi: 10.1007/BF02405102. [DOI] [PubMed] [Google Scholar]
  2. Chen T. L., Cone C. M., Feldman D. Effects of 1 alpha,25-dihydroxyvitamin D3 and glucocorticoids on the growth of rat and mouse osteoblast-like bone cells. Calcif Tissue Int. 1983 Sep;35(6):806–811. doi: 10.1007/BF02405127. [DOI] [PubMed] [Google Scholar]
  3. Chen T. L., Feldman D. Distinction between alpha-fetoprotein and intracellular estrogen receptors: evidence against the presence of estradiol receptors in rat bone. Endocrinology. 1978 Jan;102(1):236–244. doi: 10.1210/endo-102-1-236. [DOI] [PubMed] [Google Scholar]
  4. Chen T. L., Feldman D. Regulation of 1,25-dihydroxyvitamin D3 receptors in cultured mouse bone cells. Correlation of receptor concentration with the rate of cell division. J Biol Chem. 1981 Jun 10;256(11):5561–5566. [PubMed] [Google Scholar]
  5. Dodd R. C., Newman S. L., Bunn P. A., Winkler C. F., Cohen M. S., Gray T. K. Lymphokine-induced monocytic differentiation as a possible mechanism for hypercalcemia associated with adult T-cell lymphoma. Cancer Res. 1985 Jun;45(6):2501–2506. [PubMed] [Google Scholar]
  6. Forrest S. M., Ng K. W., Findlay D. M., Michelangeli V. P., Livesey S. A., Partridge N. C., Zajac J. D., Martin T. J. Characterization of an osteoblast-like clonal cell line which responds to both parathyroid hormone and calcitonin. Calcif Tissue Int. 1985 Jan;37(1):51–56. doi: 10.1007/BF02557679. [DOI] [PubMed] [Google Scholar]
  7. Gallagher J. C., Riggs B. L., DeLuca H. F. Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1980 Dec;51(6):1359–1364. doi: 10.1210/jcem-51-6-1359. [DOI] [PubMed] [Google Scholar]
  8. Kurihara N., Ishizuka S., Kiyoki M., Haketa Y., Ikeda K., Kumegawa M. Effects of 1,25-dihydroxyvitamin D3 on osteoblastic MC3T3-E1 cells. Endocrinology. 1986 Mar;118(3):940–947. doi: 10.1210/endo-118-3-940. [DOI] [PubMed] [Google Scholar]
  9. Kurihara Y., Shibata K. Effect of cortisone and estradiol on growing bones of intact and parathyroidectomized rats. Gunma J Med Sci. 1966 Jun;15(2):121–130. [PubMed] [Google Scholar]
  10. Kusuhara S., Schraer H. Cytology and autoradiography of estrogen-induced differentiation of avian endosteal cells. Calcif Tissue Int. 1982 Jul;34(4):352–358. doi: 10.1007/BF02411267. [DOI] [PubMed] [Google Scholar]
  11. Lindsay R., Hart D. M., Aitken J. M., MacDonald E. B., Anderson J. B., Clarke A. C. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet. 1976 May 15;1(7968):1038–1041. doi: 10.1016/s0140-6736(76)92217-0. [DOI] [PubMed] [Google Scholar]
  12. Liskova-Kiar Effect of estradiol benzoate on the proliferation of osteogenic cells in fetal rat fibulae cultured in vitro. Rev Can Biol. 1978 Mar;37(1):35–41. [PubMed] [Google Scholar]
  13. Majeska R. J., Rodan G. A. The effect of 1,25(OH)2D3 on alkaline phosphatase in osteoblastic osteosarcoma cells. J Biol Chem. 1982 Apr 10;257(7):3362–3365. [PubMed] [Google Scholar]
  14. Manolagas S. C., Spiess Y. H., Burton D. W., Deftos L. J. Mechanism of action of 1,25-dihydroxyvitamin D3-induced stimulation of alkaline phosphatase in cultured osteoblast-like cells. Mol Cell Endocrinol. 1983 Nov;33(1):27–36. doi: 10.1016/0303-7207(83)90054-0. [DOI] [PubMed] [Google Scholar]
  15. Martin T. J., Ingleton P. M., Coulton L. A., Melick R. A. Metabolic properties of hormonally responsive osteogenic sarcoma cells. Clin Orthop Relat Res. 1979 May;(140):247–254. [PubMed] [Google Scholar]
  16. Miller S. C., Bowman B. M. Medullary bone osteogenesis following estrogen administration to mature male Japanese quail. Dev Biol. 1981 Oct 15;87(1):52–63. doi: 10.1016/0012-1606(81)90060-9. [DOI] [PubMed] [Google Scholar]
  17. Nutik G., Cruess R. L. Estrogen receptors in bone. An evaluation of the uptake of estrogen into bone cells. Proc Soc Exp Biol Med. 1974 May;146(1):265–268. doi: 10.3181/00379727-146-38084. [DOI] [PubMed] [Google Scholar]
  18. Partridge N. C., Alcorn D., Michelangeli V. P., Kemp B. E., Ryan G. B., Martin T. J. Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells. Endocrinology. 1981 Jan;108(1):213–219. doi: 10.1210/endo-108-1-213. [DOI] [PubMed] [Google Scholar]
  19. Riggs B. L., Wahner H. W., Dunn W. L., Mazess R. B., Offord K. P., Melton L. J., 3rd Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328–335. doi: 10.1172/JCI110039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rodan S. B., Fischer M. K., Egan J. J., Epstein P. M., Rodan G. A. The effect of dexamethasone on parathyroid hormone stimulation of adenylate cyclase in ROS 17/2.8 cells. Endocrinology. 1984 Sep;115(3):951–958. doi: 10.1210/endo-115-3-951. [DOI] [PubMed] [Google Scholar]
  21. SIMMONS D. J. Cellular changes in the bones of mice as studied with tritiated thymidine and the effects of estrogen. Clin Orthop Relat Res. 1963;26:176–189. [PubMed] [Google Scholar]
  22. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  23. Seaman W. E., Gindhart T. D., Greenspan J. S., Blackman M. A., Talal N. Natural killer cells, bone, and the bone marrow: studies in estrogen-treated mice and in congenitally osteopetrotic (mi/mi) mice. J Immunol. 1979 Jun;122(6):2541–2547. [PubMed] [Google Scholar]
  24. Simmons D. J. Collagen formation and endochondral ossification in estrogen treated mice. Proc Soc Exp Biol Med. 1966 Apr;121(4):1165–1168. doi: 10.3181/00379727-121-30996. [DOI] [PubMed] [Google Scholar]
  25. Stock J. L., Coderre J. A., Mallette L. E. Effects of a short course of estrogen on mineral metabolism in postmenopausal women. J Clin Endocrinol Metab. 1985 Oct;61(4):595–600. doi: 10.1210/jcem-61-4-595. [DOI] [PubMed] [Google Scholar]
  26. Talmage R. V., Stinnett S. S., Landwehr J. T., Vincent L. M., McCartney W. H. Age-related loss of bone mineral density in non-athletic and athletic women. Bone Miner. 1986 Apr;1(2):115–125. [PubMed] [Google Scholar]
  27. Weisbrode S. E., Capen C. C. The ultrastructural effect of estrogens on bone cells in thyroparathyroidectomized rats. Am J Pathol. 1977 May;87(2):311–322. [PMC free article] [PubMed] [Google Scholar]
  28. Yoshioka T., Sato B., Matsumoto K., Ono K. Steroid receptors in osteoblasts. Clin Orthop Relat Res. 1980 May;(148):297–303. [PubMed] [Google Scholar]
  29. van Paassen H. C., Poortman J., Borgart-Creutzburg I. H., Thijssen J. H., Duursma S. A. Oestrogen binding proteins in bone cell cytosol. Calcif Tissue Res. 1978 Aug 18;25(3):249–254. doi: 10.1007/BF02010778. [DOI] [PubMed] [Google Scholar]

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