Sex Steroid Effects on Bone Metabolism

Dynamics of Bone and Cartilage Metabolism

Volumn , Issue , 2006, Pages 327-343

  Monroe, David G ^a   Spelsberg, Thomas C ^a   Khosla, S ^b  

^a Mayo Clinic   (United States)

^b WORLD HEALTH ORGANIZATION   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84861087366     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-012088562-6/50020-0     Document Type: Chapter

References (188)

1. Monroe D.G., Spelsberg T. General mechanisms of steroid receptors and receptor coregulator action. Advances in Molecular and Cell Biology 2004, Vol. 34:39-48. Elsevier B.V., Amsterdam. 34th ed. V. Miller, M. Hay (Eds.).
2. Hsueh A.J.W., Billig H. Ovarian hormone synthesis and mechanism of action. Endocrinology 1995, 2019-2030. W.B. Saunders, Philadelphia, PA. L.J. DeGroot, M. Besser, H.G. Burger, J.L. Jameon, D.L. Loriaux, J.C. Marshall, W.D. Odell, J.T. Potts, A.H. Rubenstein (Eds.).
3. Simpson E.R., Mahendroo M.S., Means G.D., Kilgore M.W., Hinshelwood M.M., Graham-Lorence S., Amarneh B., Ito Y., Fisher C.R., Michael M.D., Mendelson C.R., Bulun S.E. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr. Rev. 1994, 15(3):342-355.
4. Simpson E.R. Sources of estrogen and their importance. J. Steroid Biochem. Mol. Biol. 2003, 86(3-5):225-230.
5. Nawata H., Tanaka S., Takayanagi R., Sakai Y., Yanase T., Ikuyama S., Haji M. Aromatase in bone cell: association with osteoporosis in postmenopausal women. J. Steroid Biochem. Mol. Biol. 1995, 53(1-6):165-174.
6. Dinneen S., Alzaid A., Miles J., Rizza R. Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans. J. Clin. Invest. 1993, 92(5):2283-2290.
7. Bodine P.V., Riggs B.L., Spelsberg T.C. Regulation of c-fos expression and TGF-beta production by gonadal and adrenal androgens in normal human osteoblastic cells. J. Steroid Biochem. Mol. Biol. 1995, 52(2):149-158.
8. Manni A., Pardridge W.M., Cefalu W., Nisula B.C., Bardin C.W., Santner S.J., Santen R.J. Bioavailability of albumin-bound testosterone. J. Clin. Endocrinol. Metab. 1985, 61(4):705-710.
9. Cekan S.Z., Xing S., Ritzen M. On the binding of steroid sulfates to albumin. Experientia 1984, 40(9):949-951.
10. Monroe D.G., Spelsberg T.C. Gonadal steroids and receptors. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism 2004, 32-38. Lippincott, Williams and Wilkins, Philadelphia, PA. 5th ed. M.J. Favus (Ed.).
11. Monroe D.G., Spelsberg T.C. A case for estrogen receptors on cell membranes and nongenomic actions of estrogen. Calcif. Tissue Int. 2003, 72(3):183-184.
12. Monroe D.G., Secreto F.J., Spelsberg T. Overview of estrogen action in osteoblasts: Role of the ligand, receptor, and the coregulators. J. Musculoskeletal Neuronal. Int. 2003, 3(4):357-362.
13. Pratt W.B., Toft D.O. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp. Biol. Med. (Maywood) 2003, 228(2):111-133.
14. Smith D.F., Toft D.O. Steroid receptors and their associated proteins. Mol. Endocrinol. 1993, 7(1):4-11.
15. Cowley S.M., Hoare S., Mosselman S., Parker M.G. Estrogen receptors alpha and beta form heterodimers on DNA. J. Biol. Chem. 1997, 272(32):19858-19862.
16. Jisa E., Jungbauer A. Kinetic analysis of estrogen receptor homo-and heterodimerization in vitro. J. Steroid Biochem. Mol. Biol. 2003, 84(2-3):141-148.
17. Tsai S.Y., Carlstedt-Duke J., Weigel N.L., Dahlman K., Gustafsson J.A., Tsai M.J., O'Malley B.W. Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation. Cell 1988, 55(2):361-369.
18. Driggers P.H., Segars J.H. Estrogen action and cytoplasmic signaling pathways. Part II: the role of growth factors and phosphorylation in estrogen signaling. Trends Endocrinol. Metab. 2002, 13(10):422-427.
19. Lannigan D.A. Estrogen receptor phosphorylation. Steroids 2003, 68(1):1-9.
20. Takimoto G.S., Tasset D.M., Eppert A.C., Horwitz K.B. Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: analysis with zinc finger mutants and the progesterone antagonist ZK98299. Proc. Natl Acad. Sci. USA 1992, 89(7):3050-3054.
21. Smith C.L., O'Malley B.W. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev. 2004, 25(1):45-71.
22. McDonnell D.P., Norris J.D. Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone. Osteoporos. Int. 1997, 7(Suppl 1):S29-S34.
23. Kousteni S., Bellido T., Plotkin L.I., O'Brien C.A., Bodenner D.L., Han L., Han K., DiGregorio G.B., Katzenellenbogen J.A., Katzenellenbogen B.S., Roberson P.K., Weinstein R.S., Jilka R.L., Manolagas S.C. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 2001, 104(5):719-730.
24. Kousteni S., Chen J.R., Bellido T., Han L., Ali A.A., O'Brien C.A., Plotkin L., Fu Q., Mancino A.T., Wen Y., Vertino A.M., Powers C.C., Stewart S.A., Ebert R., Parfitt A.M., Weinstein R.S., Jilka R.L., Manolagas S.C. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 2002, 298(5594):843-846.
25. Kousteni S., Han L., Chen J.R., Almeida M., Plotkin L.I., Bellido T., Manolagas S.C. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J. Clin. Invest. 2003, 111(11):1651-1664.
26. Parl F.F. Estrogen Receptor and Breast Cancer 2000, IOS Press, Amsterdam.
27. Kuiper G.G., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J.A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl Acad. Sci. USA 1996, 93(12):5925-5930.
28. Arts J., Kuiper G.G., Janssen J.M., Gustafsson J.A., Lowik C.W., Pols H.A., van Leeuwen J.P. Differential expression of estrogen receptors alpha and beta mRNA during differentiation of human osteoblast SV-HFO cells. Endocrinology 1997, 138(11):5067-5070.
29. Onoe Y., Miyaura C., Ohta H., Nozawa S., Suda T. Expression of estrogen receptor beta in rat bone. Endocrinology 1997, 138(10):4509-4512.
30. Sims N.A., Clement-Lacroix P., Minet D., Fraslon-Vanhulle C., Gaillard-Kelly M., Resche-Rigon M., Baron R. A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor-deficient mice. J. Clin. Invest. 2003, 111(9):1319-1327.
31. Sims N.A., Dupont S., Krust A., Clement-Lacroix P., Minet D., Resche-Rigon M., Gaillard-Kelly M., Baron R. Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-beta in bone remodeling in females but not in males. Bone 2002, 30(1):18-25.
32. Onate S.A., Tsai S.Y., Tsai M.J., O'Malley B.W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 1995, 270(5240):1354-1357.
33. McKenna N.J., Lanz R.B., O'Malley B.W. Nuclear receptor coregulators: cellular and molecular biology. Endocr. Rev. 1999, 20(3):321-344.
34. Voegel J.J., Heine M.J., Zechel C., Chambon P., Gronemeyer H. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. Embo. J. 1996, 15(14):3667-3675.
35. Li H., Gomes P.J., Chen J.D. RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc. Natl Acad. Sci. USA 1997, 94(16):8479-8484.
36. Xu J., Qiu Y., DeMayo F.J., Tsai S.Y., Tsai M.J., O'Malley B.W. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 1998, 279(5358):1922-1925.
37. Modder U.I., Samyal A., Kearns A.E., Sibonga J.D., Nishihara E., Xu J., O'Malley B.W., Ritman E.L., Riggs B.L., Spelsberg T.C., Khosla S. Effects of loss of steroid receptor coactivator-1 on the skeletal response to estrogen in mice. Endocrinology 2004, 145(2):913-921.
38. Xu J., Liao L., Ning G., Yoshida-Komiya H., Deng C., O'Malley B.W. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIBI/ACTR/TRAM-1) is required for normal growth, puberty female reproductive function, and mammary gland development. Proc. Natl Acad. Sci. USA 2000, 97(12):6379-6384.
39. Martini P.G., Katzenellenbogen B.S. Modulation of estrogen receptor activity by selective coregulators. J. Steroid Biochem. Mol. Biol. 2003, 85(2-5):117-122.
40. Heery D.M., Kalkhoven E., Hoare S., Parker M.G. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 1997, 387(6634):733-736.
41. Leo C., Chen J.D. The SRC family of nuclear receptor coactivators. Gene 2000, 245(1):1-11.
42. Monroe D.G., Johnsen S.A., Subramaniam M., Getz B.J., Khosla S., Riggs B.L., Spelsberg T.C. Mutual antagonism of estrogen receptors alpha and beta and their preferred interactions with steroid receptor coactivators in human osteoblastic cell lines. J. Endocrinol. 2003, 176(3):349-357.
43. Riggs B.L., Khosla S., Melton L.J. Sex steroids and the construction and conservation of the adult skeleton. Endocr. Rev. 2002, 23(3):279-302.
44. Riggs B.L., Wahner H.W., Melton L.J., Richelson L.S., Judd H.L., Offord K.P. Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. J. Clin. Invest. 1986, 77(5):1487-1491.
45. Eriksen E.F., Colvard D.S., Berg N.J., Graham M.L., Mann K.G., Spelsberg T.C., Riggs B.L. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988, 241(4861):84-86.
46. Gyda M., Corisdeo S., Zaidi M., Troen B.R. Macrophage colony-stimulating factor suppresses osteoblast formation. Biochem. Biophys. Res. Commun. 2001, 285(2):328-334.
47. Hoyland J.A., Mee A.P., Baird P., Braidman I.P., Mawer E.B., Freemont A.J. Demonstration of estrogen receptor mRNA in bone using in situ reverse-transcriptase polymerase chain reaction. Bone 1997, 20(2):87-92.
48. Vidal O., Kindblom L.G., Ohlsson C. Expression and localization of estrogen receptor-beta in murine and human bone. J. Bone Miner. Res. 1999, 14(6):923-929.
49. Oursler M.J., Pederson L., Fitzpatrick L., Riggs B.L., Spelsberg T. Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells. Proc. Natl Acad. Sci. USA 1994, 91(12):5227-5231.
50. Riggs B.L., Melton L.J. The prevention and treatment of osteoporosis [published erratum appears in N. Engl. J. Med. 1993 Jan 7: 328(1):65]. N. Engl. J. Med. 1992, 327:620-627.
51. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001, 142(12):5050-5055.
52. Hofbauer L.C., Khosla S., Dunstan C.R., Lacey D.L., Boyle W.J., Riggs B.L. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J. Bone Miner. Res. 2000, 15(1):2-12.
53. Troen B.R. Molecular mechanisms underlying osteoclast formation and activation. Exp. Gerontol. 2003, 38(6):605-614.
54. Bell N.H. Advances in the treatment of osteoporosis. Curr. Drug. Targets Immune Endocr. Metabol. Disord. 2001, 1(1):93-102.
55. Bord S., Ireland D.C., Beavan S.R., Compston J.E. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 2003, 32(2):136-141.
56. Hofbauer L.C., Khosla S., Dunstan C.R., Lacey D.L., Spelsberg T.C., Riggs B.L. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 1999, 140(9):4367-4370.
57. 2 and progesterone on the expression of osteoprotegerin in normal human osteoblast-like cells. J. Endocrinol. Invest. 2002, 25(9):785-790.
58. Saika M., Inoue D., Kido S., Matsumoto T. 17?-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha. Endocrinology 2001, 142(6):2205-2212.
59. Eghbali-Fatourechi G., Khosla S., Sanyal A., Boyle W.J., Lacey D.L., Riggs B.L. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J. Clin. Invest. 2003, 111(8):1221-1230.
60. Srivastava S., Toraldo G., Weitzmann M.N., Cenci S., Ross F.P., Pacifici R. Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-?B ligand (RANKL)-induced JNK activation. J. Biol. Chem. 2001, 276(12):8836-8840.
61. Kanatani M., Sugimoto T., Takahashi Y., Kaji H., Kitazawa R., Chihara K. Estrogen via the estrogen receptor blocks cAMP-mediated parathyroid hormone (PTH)-stimulated osteoclast formation. J. Bone Miner. Res. 1998, 13(5):854-862.
62. Manolagas S.C., Jilka R.L. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N. Engl. J. Med. 1995, 332(5):305-311.
63. Pacifici R., Brown C., Puscheck E., Friedrich E., Slatopolsky E., Maggio D., McCracken R., Avioli L.V. Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc. Natl Acad. Sci. USA 1991, 88(12):5134-5138.
64. Tanaka S., Takahashi N., Udagawa N., Tamura T., Akatsu T., Stanley E.R., Kurokawa T., Suda T. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J. Clin. Invest. 1993, 91(1):257-263.
65. Kimble R.B., Vannice J.L., Bloedow D.C., Thompson R.C., Hopfer W., Kung V.T., Brownfield C., Pacifici R. Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats. J. Clin. Invest. 1994, 93(5):1959-1967.
66. Ammann P., Rizzoli R., Bonjour J.P., Bourrin S., Meyer J.M., Vassalli P., Garcia I. Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J. Clin. Invest. 1997, 99(7):1699-1703.
67. Kimble R.B., Srivastava S., Ross F.P., Matayoshi A., Pacifici R. Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1 and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production. J. Biol. Chem. 1996, 271(46):28890-28897.
68. Nanes M.S. Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene 2003, 321:1-15.
69. Kitazawa R., Kimble R.B., Vannice J.L., Kung V.T., Pacifici R. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. J. Clin. Invest. 1994, 94(6):2397-2406.
70. Manolagas S.C., Kousteni S., Jilka R.L. Sex steroids and bone. Recent Prog Horm. Res. 2002, 57:385-409.
71. Girasole G., Jilka R.L., Passeri G., Boswell S., Boder G., Williams D.C., Manolagas S.C. 17?-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J. Clin. Invest. 1992, 89(3):883-891.
72. Jilka R.L., Hangoc G., Girasole G., Passeri G., Williams D.C., Abrams J.S., Boyce B., Broxmeyer H., Manolagas S.C. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 1992, 257(5066):88-91.
73. Kassem M., Harris S.A., Spelsberg T.C., Riggs B.L. Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors. J. Bone Miner. Res. 1996, 11(2):193-199.
74. Poli V., Balena R., Fattori E., Markatos A., Yamamoto M., Tanaka H., Ciliberto G., Rodan G.A., Costantini F. Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. Embo. J. 1994, 13(5):1189-1196.
75. Ivey J.L., Baylink D.J. Postmenopausal osteoporosis: proposed roles of defective coupling and estrogen deficiency. Metab. Bone Dis. Relat. Res. 1981, 3(1):3-7.
76. Ernst M., Heath J.K., Rodan G.A. Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-1, and parathyroid hormone-stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones. Endocrinology 1989, 125(2):825-833.
77. Oursler M.J., Cortese C., Keeting P., Anderson M.A., Bonde S.K., Riggs B.L., Spelsberg T.C. Modulation of transforming growth factor-beta production in normal human osteoblast-like cells by 17?-estradiol and parathyroid hormone. Endocrinology 1991, 129(6):3313-3320.
78. Brincat M., Moniz C.F., Kabalan S., Versi E., O'Dowd T., Magos A.L., Montgomery J., Studd J.W. Decline in skin collagen content and metacarpal index after the menopause and its prevention with sex hormone replacement. Br. J. Obstet. Gynaecol. 1987, 94(2):126-129.
79. Kawaguchi H., Pilbeam C.C., Vargas S.J., Morse E.E., Lorenzo J.A., Raisz L.G. Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae. J. Clin. Invest. 1995, 96(1):539-548.
80. Westerlind K.C., Wakley G.K., Evans G.L., Turner R.T. Estrogen does not increase bone formation in growing rats. Endocrinology 1993, 133(6):2924-2934.
81. Gray C., Colston K.W., Mackay A.G., Taylor M.L., Arnett T.R. Interaction of androgen and 1,25-dihydroxyvitamin D3: effects on normal rat bone cells. J. Bone Miner. Res. 1992, 7(1):41-46.
82. Gray T.K., Mohan S., Linkhart T.A., Baylink D.J. Estradiol stimulates in vitro the secretion of insulin-like growth factors by the clonal osteoblastic cell line, UMR106. Biochem. Biophys. Res. Commun. 1989, 158(2):407-412.
83. Monroe D.G., Getz B.J., Johnsen S.A., Riggs B.L., Khosla S., Spelsberg T.C. Estrogen receptor isoform-specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ER ? or ER?. J. Cell Biochem. 2003, 90(2):315-326.
84. Kassem M., Okazaki R., De Leon D., Harris S.A., Robinson J.A., Spelsberg T.C., Conover C.A., Riggs B.L. Potential mechanism of estrogen-mediated decrease in bone formation: estrogen increases production of inhibitory insulin-like growth factor-binding protein-4. Proc. Assoc. Am. Physicians 1996, 108(2):155-164.
85. Robinson J.A., Harris S.A., Riggs B.L., Spelsberg T.C. Estrogen regulation of human osteoblastic cell proliferation and differentiation. Endocrinology 1997, 138(7):2919-2927.
86. Waters K.M., Rickard D.J., Riggs B.L., Khosla S., Katzenellenbogen J.A., Katzenellenbogen B.S., Moore J., Spelsberg T.C. Estrogen regulation of human osteoblast function is determined by the stage of differentiation and the estrogen receptor isoform. J. Cell Biochem. 2001, 83(3):448-462.
87. Cao L., Bu R., Oakley J.I., Kalla S.E., Blair H.C. Estrogen receptor-? modulates synthesis of bone matrix proteins in human osteoblast-like MG63 cells. J. Cell. Biochem. 2003, 89(1):152-164.
88. Kian Tee M., Rogatsky I., Tzagarakis-Foster C., Cvoro A., An J., Christy R.J., Yamamoto K.R., Leitman D.C. Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol. Biol. Cell 2004, 15(3):1262-1272.
89. Stossi F., Barnett D.H., Frasor J., Komm B., Lyttle C.R., Katzenellenbogen B.S. Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (alpha) or estrogen receptor (beta) in human osteosarcoma cells: Distinct and common target genes for these receptors. Endocrinology 2004, 145(7):3473-3486.
90. Tomkinson A., Reeve J., Shaw R.W., Noble B.S. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J. Clin. Endocrinol. Metab. 1997, 82(9):3128-3135.
91. Pitsillides A.A., Rawlinson S.C., Suswillo R.F., Bourrin S., Zaman G., Lanyon L.E. Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling?. Faseb. J. 1995, 9(15):1614-1622.
92. Bonjour J.P., Theintz G., Buchs B., Slosman D., Rizzoli R. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J. Clin. Endocrinol. Metab. 1991, 73(3):555-563.
93. Gustafsson P.O., Kasstrom H., Lindberg L., Olsson S.E. Growth and mitotic rate of the proximal tibial epiphyseal plate in hypophysectomized rats given estradiol and human growth hormone. Acta Radiol. Suppl. 1975, 344:69-74.
94. Strickland A.L., Sprinz H. Studies of the influence of estradiol and growth hormone on the hypophysectomized immature rat epiphyseal cartilage growth plate. Am. J. Obstet. Gynecol. 1973, 115(4):471-477.
95. Ho K.K., Weissberger A.J. Impact of short-term estrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism. J. Bone Miner. Res. 1992, 7(7):821-827.
96. Delmas P.D., Bjarnason N.H., Mitlak B.H., Ravoux A.C., Shah A.S., Huster W.J., Draper M., Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N. Engl. J. Med. 1997, 337(23):1641-1647.
97. Brzozowski A.M., Pike A.C., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.A., Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389(6652):753-758.
98. Tamrazi A., Carlson K.E., Katzenellenbogen J.A. Molecular sensors of estrogen receptor conformations and dynamics. Mol. Endocrinol. 2003, 17(12):2593-2602.
99. Heldring N., Nilsson M., Buehrer B., Treuter E., Gustafsson J.A. Identification of tamoxifen-induced coregulator interaction surfaces within the ligand-binding domain of estrogen receptors. Mol. Cell. Biol. 2004, 24(8):3445-3459.
100. Ray A., Prefontaine K.E., Ray P. Down-regulation of the interleukin-6 promoter by estrogen is mediated by NF-?B and C/EBP. J. Biol. Chem. 1994, 269:12940-12946.
101. Stein B., Yang M.X. Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol. Cell. Biol. 1995, 15(9):4971-4979.
102. Yang N.N., Venugopalan M., Hardikar S., Glasebrook A. Identification of an estrogen response element activated by metabolites of 17?-estradiol and raloxifene. Science 1996, 273(5279):122211225.
103. Yang N.N., Bryant H.U., Hardikar S., Sato M., Galvin R.J., Glasebrook A.L., Termine J.D. Estrogen and raloxifene stimulate transforming growth factor-?3 gene expression in rat bone: a potential mechanism for estrogen- or raloxifene-mediated bone maintenance. Endocrinology 1996, 137(5):2075-2084.
104. Paech K., Webb P., Kuiper G.G., Nilsson S., Gustafsson J., Kushner P.J., Scanlan T.S. Differential ligand activation of estrogen receptors ER? and ER? at AP1 sites. Science 1997, 277(5331):1508-1510.
105. Kuiper G.G., Gustafsson J.A. The novel estrogen receptor-beta subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens. FEBS Lett. 1997, 410(1):87-90.
106. Kuiper G.G., Carlsson B., Grandien K., Enmark E., Haggblad J., Nilsson S., Gustafsson J.A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997, 138(3):863-870.
107. MacNamara P., O'Shaughenssy C., Manduca P., Loughrey H.C. Progesterone receptors are expressed in human osteoblast-like cell lines and in primary human osteoblast cultures. Calcif. Tissue Int. 1995, 57(6):436-441.
108. Wei L.L., Leach M.W., Miner R.S., Demers L.M. Evidence for progesterone receptors in human osteoblast-like cells. Biochem. Biophys. Res. Commun. 1993, 195(2):525-532.
109. Flototto T., Niederacher D., Hohmann D., Heimerzheim T., Dall P., Djahansouzi S., Bender H.G., Hanstein B. Molecular mechanism of estrogen receptor (ER) alpha-specific, estradioldependent expression of the progesterone receptor (PR) B-isoform. J. Steroid Biochem. Mol. Biol. 2004, 88(2):131-142.
110. Rickard D.J., Waters K.M., Ruesink T.J., Khosla S., Katzenellenbogen J.A., Katzenellenbogen B.S., Riggs B.L., Spelsberg T.C. Estrogen receptor isoform-specific induction of progesterone receptors in human osteoblasts. J. Bone Miner. Res. 2002, 17(4):580-592.
111. Tremollieres F.A., Strong D.D., Baylink D.J., Mohan S. Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production. Acta Endocrinol. (Copenh.) 1992, 126(4):329-337.
112. Azizi G., Hansen A., Prestwood K.M. Effect of micronized progesterone on bone turnover in postmenopausal women on estrogen replacement the rapy. Endocr. Res. 2003, 29(2):133-140.
113. Luo X.H., Liao E.Y., Su X. Progesterone upregulates TGF-? isoforms (?1, ?2, and ?3) expression in normal human osteoblast-like cells. Calcif. Tissue Int. 2002, 71(4):329-334.
114. Prior J.C., Vigna Y.M., Wark J.D., Eyre D.R., Lentle B.C., Li D.K., Ebeling P.R., Atley L. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. J. Bone Miner. Res. 1997, 12(11):1851-1863.
115. Colvard D.S., Eriksen E.F., Keeting P.E., Wilson E.M., Lubahn D.B., French F.S., Riggs B.L., Spelsberg T.C. Identification of androgen receptors in normal human osteoblast-like cells. Proc. Natl Acad. Sci. USA 1989, 86(3):854-857.
116. Sanchez-Visconti G., Herrero L., Rabadan M., Pereira I., Ruiz-Torres A. Ageing and prostate: age-related changes in androgen receptors of epithelial cells from benign hypertrophic glands compared with cancer. Mech. Ageing Dev. 1995, 82(1):19-29.
117. Schweikert H.U., Rulf W., Niederle N., Schafer H.E., Keck E., Kruck F. Testosterone metabolism in human bone. Acta Endocrinol. (Copenh.) 1980, 95(2):258-264.
118. Nakano Y., Morimoto I., Ishida O., Fujihira T., Mizokami A., Tanimoto A., Yanagihara N., Izumi F., Eto S. The receptor, metabolism and effects of androgen in osteoblastic MC3T3-El cells. Bone Miner. 1994, 26(3):245-259.
119. Stepan J.J., Lachman M., Zverina J., Pacovsky V., Baylink D.J. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J. Clin. Endocrinol. Metab. 1989, 69(3):523-527.
120. Tenover J.S. Effects of testosterone supplementation in the aging male. J. Clin. Endocrinol. Metab. 1992, 75(4):1092-1098.
121. Anderson F.H., Francis R.M., Peaston R.T., Wastell H.J. Androgen supplementation in eugonadal men with osteoporosis: effects of six months' treatment on markers of bone formation and resorption. J. Bone Miner. Res. 1997, 12(3):472-478.
122. Riggs B.L., Jowsey J., Goldsmith R.S., Kelly P.J., Hoffman D.L., Arnaud C.D. Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis. J. Clin. Invest. 1972, 51(7):1659-1663.
123. Pederson L., Kremer M., Judd J., Pascoe D., Spelsberg T.C., Riggs B.L., Oursler M.J. Androgens regulate bone resorption activity of isolated osteoclasts in vitro. Proc. Natl Acad. Sci. USA 1999, 96(2):505-510.
124. Pilbeam C.C., Raisz L.G. Effects of androgens on parathyroid hormone and interleukin-1-stimulated prostaglandin production in cultured neonatal mouse calvariae. J. Bone Miner. Res. 1990, 5(11):1183-1188.
125. Bellido T., Jilka R.L., Boyce B.F., Girasole G., Broxmeyer H., Dalrymple S.A., Murray R., Manolagas S.C. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. J. Clin. Invest. 1995, 95(6):2886-2895.
126. Hofbauer L.C., Ten R.M., Khosla S. The anti-androgen hydroxyflutamide and androgens inhibit interleukin-6 production by an androgen-responsive human osteoblastic cell line. J. Bone Miner. Res. 1999, 14(8):1330-1337.
127. Raisz L.G., Wiita B., Artis A., Bowen A., Schwartz S., Trahiotis M., Shoukri K., Smith J. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J. Clin. Endocrinol. Metab. 1996, 81(1):37-43.
128. Baran D.T., Bergfeld M.A., Teitelbaum S.L., Avioli L.V. Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male. Calcif. Tissue Res. 1978, 26(2):103-106.
129. Cantatore F.P., Carrozzo M., Magli D., D'Amore M., Pipitone V. Serum osteocalcin levels in normal humans of different sex and age. An epidemiological study. Panminerva Med. 1988, 30(1):23-25.
130. Morley J.E., Perry H.M., Kaiser F.E., Kraenzle D., Jensen J., Houston K., Mattammal M., Perry H.M. Effects of testosterone replacement therapy in old hypo gonadal males: a preliminary study. J. Am. Geriatr. Soc. 1993, 41(2):149-152.
131. Kasperk C.H., Wergedal J.E., Farley J.R., Linkhart T.A., Turner R.T., Baylink D.J. Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 1989, 124(3):1576-1578.
132. Benz D.J., Haussler M.R., Thomas M.A., Speelman B., Komm B.S. High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblastlike osteosarcoma cells. Endo crinology 1991, 128(6):2723-2730.
133. Hofbauer L.C., Hicok K.C., Khosla S. Effects of gonadal and adrenal androgens in a novel androgen-responsive human osteoblastic cell line. J. Cell. Biochem. 1998, 71(1):96-108.
134. Kasperk C.H., Faehling K., Borcsok I., Ziegler R. Effects of androgens on subpopulations of the human osteosarcomacell line SaOS2. Calcif. Tissue Int. 1996, 58(5):376-382.
135. Kasperk C.H., Wakley G.K., Hierl T., Ziegler R. Gonadal and adrenal and rogens are potent regulators of human bone cell metabolism in vitro. J. Bone Miner. Res. 1997, 12(3):464-471.
136. Kasperk C., Fitzsimmons R., Strong D., Mohan S., Jennings J., Wergedal J., Baylink D. Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells. J. Clin. Endocrinol. Metab. 1990, 71(5):1322-1329.
137. Gori F., Hofbauer L., Conover C.A., Khosla S. Effects of androgens on the insulin-like growth factor system in an and rogen -responsive human osteoblastic cell line. Endocrinology 1999, 140:5579-5586.
138. Durbidge T.C., Morris H.A., Parsons A.M., Parkinson I.H., Moore R.J., Porter S., Need A.G., Nordin B.E., Vernon-Roberts B. Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy. Calcif. Tissue Int. 1990, 47(6):383-387.
139. Turner R.T., Lifrak E.T., Beckner M., Wakley G.K., Hannon K.S., Parker L.N. Dehydroepiandrosterone reduces cancellous bone osteopenia in ovariectomized rats. Am. J. Physiol. 1990, 258(4 Pt 1):E673-E677.
140. Labrie F., Belanger A., Simard J., Van L.-T., Labrie C. DHEA and peripheral androgen and estrogen formation: intracinology. Ann. N.Y. Acad. Sci. 1995, 774:16-28.
141. Meikle A.W., Dorchuck R.W., Araneo B.A., Stringham J.D., Evans T.G., Spruance S.L., Daynes R.A. The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells. J. Steroid Biochem. Mol. Biol. 1992, 42(3-4):293-304.
142. Lu P.W., Briody J.N., Ogle G.D., Morley K., Humphries I.R., Allen J., Howman-Giles R., Sillence D., Cowell C.T. Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study. J. Bone Miner. Res. 1994, 9(9):1451-1458.
143. Riis B.J., Krabbe S., Christiansen C., Catherwood B.D., Deftos L.J. Bone turnover in male puberty: a longitudinal study. Calcif. Tissue. Int. 1985, 37(3):213-217.
144. Parker L.N. Adrenarche. Endocrinol. Metab. Clin. North Am. 1991, 20(1):71-83.
145. Slemenda C.W., Reister T.K., Hui S.L., Miller J.Z., Christian J.C., Johnston C.C. In fluences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity. J. Pediatr. 1994, 125(2):201-207.
146. Fehily A.M., Coles R.J., Evans W.D., Elwood P.C. Factors affecting bone density in young adults. Am. J. Clin. Nutr. 1992, 56(3):579-586.
147. Mauras N., Haymond M.W., Darmaun D., Vieira N.E., Abrans S.A., Yergey A.L. Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone. J. Clin. Invest. 1994, 93(3):1014-1019.
148. Hobbs C.J., Plymate S.R., Rosen C.J., Adler R.A. Testosterone administration increases insulin-like growth factor-1 levels in normal men. J. Clin. Endocrinol. Metab. 1993, 77(3):776-779.
149. Smith E.P., Boyd J., Frank G.R., Takahashi H., Cohen R.M., Specker B., Williams T.C., Lubahn D.B., Korach K.S. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 1994, 331(16):1056-1061.
150. Morishima A., Grumbach M.M., Simpson E.R., Fisher C., Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J. Clin. Endocrinol. Metab. 1995, 80(12):3689-3698.
151. Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., Korach K.S., Simoni E.R., Faustini-Fustini M., Serpente S., Boyd J., Korach K.S., Simpson E.R. Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med. 1997, 337(2):91-95.
152. Morishima A., Grumbach M.M., Bilezikian J.P. Estrogen markedly increases bone mass in an estrogen deficient young man with aromatase deficiency. J. Bone Miner. Res. 1997, 12(Suppl 1):S126.
153. Center J.R., Nguyen T.V., White C.P., Eisman J.A. Male osteoporosis
154. Greendale G.A., Edelstein S., Barrett-Connor E. Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J. Bone Miner. Res. 1997, 12(11):1833-1843.
155. Khosla S., Melton L.J., Atkinson E.J., O'Fallon W.M., Klee G.G., Riggs B.L. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J. Clin. Endocrinol. Metab. 1998, 83(7):2266-2274.
156. Slemenda C.W., Longcope C., Zhou L., Hui S.L., Peacock M., Johnston C.C. Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J. Clin. Invest. 1997, 100(7):1755-1759.
157. Amin S., Zhang Y., Sawin C.T., Evans S.R., Hamnan M.T., Kiel D.P., Wilson P.W., Felson D.T. Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study. Ann. Intern. Med. 2000, 133(12):951-963.
158. Khosla S., Melton L.J., Atkinson E.J., O'Fallon W.M. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J. Clin. Endocrinol. Metab. 2001, 86(8):3555-3561.
159. Gennari L., Merlotti D., Martini G., Gonnelli S., Franci B., Campagna S., Lucani B., Dal Canto N., Valenti R., Gennari C., Nuti R. Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J. Clin. Endocrinol. Metab. 2003, 88(11):5327-5333.
160. Van Pottelbergh I., Goemaere S., Kaufman J.M. Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age. J. Clin. Endocrinol Metab. 2003, 88(7):3075-3081.
161. Falahati-Nini A., Riggs B.L., Atkinson E.J., O'Fallon W.M., Eastell R., Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 2000, 106(12):1553-1560.
162. Leder B.Z., LeBlanc K.M., Schoenfeld D.A., Eastell R., Finkelstein J.S. Differential effects of androgens and estrogens on bone turnover in normal men. J. Clin. Endocrinol. Metab. 2003, 88(1):204-210.
163. Taxel P., Kennedy D.G., Fall P.M., Willard A.K., Clive J.M., Raisz L.G. The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone tumover in older men. J. Clin. Endocrinol. Metab. 2001, 86(6):2869-2874.
164. Slemenda C., Hui S.L., Longcope C., Johnston C.C. Sex steroids and bone mass. A study of changes about the time of menopause. J. Clin. Invest. 1987, 80(5):1261-1269.
165. Buchanan J.R., Hospodar P., Myers C., Leuenberger P., Demers L.M. Effect of excess endogenous androgens on bone density in young women. J. Clin. Endocrinol. Metab. 1988, 67(5):937-943.
166. 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, 51(6):1359-1364.
167. 3 in oophorectomized women. J. Clin. Endocrinol. Metab. 1990, 71(5):1288-1293.
168. Thomas M.L., Xu X., Norfleet A.M., Watson C.S. The presence of functional estrogen receptors in intestinal epithelial cells. Endocrinology 1993, 132(1):426-430.
169. Hagenfeldt Y., Eriksson H.A. The estrogen receptor in the rat kidney. Onto geny, properties and effects of gonadectomy on its concentration. J. Steroid Biochem. 1988, 31(1):49-56.
170. Forte L.R., Langeluttig S.G., Biellier H.V., Poelling R.E., Magliola L., Thomas M.L. Upregulation of kidney adenylate cyclase in the egg-laying hen: role of estrogen. Am. J. Physiol. 1983, 245(3):E273-E280.
171. Stock J.L., Coderre J.A., Burke E.M., Danner D.B., Chipman S.D., Shapiro J.R. Identification of estrogen receptor mRNA and the estrogen modulation of parathyroid hormone-stimulated cyclic AMP accumulation in opossum kidney cells. J. Cell. Physiol. 1992, 150(3):517-525.
172. Nordin B.E., Need A.G., Morris H.A., Horwitz M., Robertson W.G. Evidence for a renal calcium leak in postmenopausal women. J. Clin. Endocrinol. Metab. 1991, 72(2):401-407.
173. McKane W.R., Khosla S., Burritt M.F., Kao P.C., Wilson D.M., Ory S.J., Riggs B.L. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause-a clinical research center study. J. Clin. Endocrinol. Metab. 1995, 80(12):3458-3464.
174. Naveh-Many T., Almogi G., Livni N., Silver J. Estrogen receptors and biologic response in rat parathyroid tissue and C cells. J. Clin. Invest. 1992, 90(6):2434-2438.
175. Prince R.L., MacLaughlin D.T., Gaz R.D., Neer R.M. Lack of evidence for estrogen receptors in human and bovine parathyroid tissue. J. Clin. Endocrinol. Metab. 1991, 72(6):1226-1228.
176. Cosman F., Nieves J., Horton J., Shen V., Lindsay R. Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women. J. Clin. Endocrinol. Metab. 1994, 78(4):939-943.
177. Vincent A., Riggs B.L., Atkinson E.J., Oberg A.L., Khosla S. Effect of estrogen replacement therapy on parathyroid hormone secretion in elderly postmenopausal women. Menopause 2003, 10:165-171.
178. Duarte B., Hargis G.K., Kukreja S.C. Effects of estradiol and progesterone on parathyroid hormone secretion from human parathyroid tissue. J. Clin. Endocrinol. Metab. 1988, 66(3):584-587.
179. Hope W.G., Ibarra M.J., Thomas M.L. Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat. Proc. Soc. Exp. Biol. Med. 1992, 200(4):536-541.
180. Lafferty F.W., Spencer G.E., Pearson O.H. Effects of androgens, estrogens and high calcium intakes on bone formation and resorption in osteoporosis. Am. J. Med. 1964, 36:514-528.
181. Need A.G., Horowitz M., Morris H.A., Walker C.J., Nordin B.E. Effects of nandrolone therapy on forearm bone mineral content in osteoporosis. Clin. Orthop. 1987, 225:273-278.
182. Stefani S., Aguiari G.L., Bozza A., Maestri I., Magri E., Cavazzini P., Piva R., del Senno L. Androgen responsiveness and androgen receptor gene expression in human kidney cells in continuous culture. Biochem. Mol. Biol. Int. 1994, 32(4):597-604.
183. Goldstone A.D., Koenig H., Lu C.Y. Androgenic stimulation of endocytosis, amino acid and hexose transport in mouse kidney cortex involves increased calcium fluxes. Biochim. Biophys. Acta. 1983, 762(2):366-371.
184. Reifenstein E.C., Albright F. The metabolic effects of steroid hormones in osteoporosis. J. Clin. Invest. 1946, 26:24-56.
185. Chesnut C.H., Ivey J.L., Gruber H.E., Matthews M., Nelp W.B., Sisom K., Baylink D.J. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism 1983, 32(6):571-580.
186. Mason R.A., Morris H.A. Effects of dihydrotestosterone on bone biochemical markers in sham and oophorectomized rats. J. Bone Miner. Res. 1997, 12(9):1431-1437.
187. Riggs B.L., Khosla S., Melton L.J. Aunitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J. Bone Miner. Res. 1998, 13(5):763-773.
188. Manolagas S.C., Kousteni S. Perspective: nonreproductive sites of action of reproductive hormones. Endocrinology 2001, 142(6):2200-2204.