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Chapter 11/Androgens and Bone 229 26. Rosner W, Hryb DJ, Khan MS, et al. Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. J Steroid Biochem Mol Biol 1999;69:481–485. 27. Abu EO, Horner A, Kusec V, et al. The localization of androgen receptors in human bone. J Clin Endocrinol Metab 1997;82:3493–3497. 28. Pederson L, Kremer M, Jodd J, et al. Androgens regulate bone resorption activity of isolated osteoclasts in vitro. Proc Natl Acad Sci USA 1999;6:505–510. 29. Bland R. Steroid hormone receptor expression and action in bone. Clin Sci 2000;98:217–240. 30. Colvard DS, Eriksen EF, Keeting PE, et al. Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci USA 1989;86:854–857. 31. Benz DJ, Haussler MR, Thomas MA, et al. 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 osteoblast-like ostersarcoma cells. Endocrinol 1991;128: 2723–2730. 32. Wiren K, Keenan E, Zhang X, et al. Homologous androgen receptor up-regulation in osteoblastic cells may be associated with enhanced functional androgen responsiveness. Endocrinol 1999; 140:3114–3124. 33. Bodine PVN, Riggs BL, Spelsberg TC. Regulation of c-fos expression and TGF-β production by gonadal and adrenal androgens in normal human osteoblastic cells. J Steroid Biochem Mole Biol 1995;52:149–158. 34. Benten WP, Lieberherr M, Stamm O, et al. Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell 1999;10:3113–3123. 35. Lieberherr M, Grosse B. Androgens increase intracellular calcium concentration and inositol 1,4,5trisphosphate and diacylglycerol formation via a pertussis toxin-sensitive G-protein. J Biol Chem 1994;269:7217–7223. 36. Mizuno Y, Hosoi T, Inoue S, et al. Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells. Calcif Tissue Int 1994;54:325–326. 37. Hofbauer LC, Khosla S. Androgen effects on bone metabolism: recent progress and controversies. Eur J Endocrinol 1999;140:271–286. 38. Kaspi CH, Wakley GK, Hierl T, Ziegler R. Gonadal and androgens are potent regulators of human bone cell metabolism in vitro. J Bone Miner Res 1997;12:464–471. 39. Kasperk CH, Wergedal JE, Farley JR, et al. Androgens directly stimulate proliferation of bone cells in vitro. Endocrinol 1989;124:1576–1578. 40. Kasperk CH, Wakley GK, Hierl T, Ziegler R. Gonadal and adrenal androgens are poten regulators of human bone cell metabolism in vitro. J Bone Miner Res 1997;12:464–471. 41. Takeuchi M, Kakushi H, Tohkin M. Androgens directly stimulate mineralization and increase androgen receptors in human osteoblast-like osteoscarcoma cells. Biochem Biophysi Res Commun 1994;204:905–911. 42. Czerwiec FS, Liaw JJ, Liu SB, et al. Absence of androgen-mediated transcriptional effects in osteoblastic cells despite presence of androgen receptors. Bone 1997;21:49–56. 43. Gori F, Hofbauer LC, Conover CA, Khosla S. Effects of androgens on the insulin-like growth factor system in an androgen-responsive human osteoblastic cell line. Endocrinol 1999;140:5579–5586. 44. Kousteni S, Bellido T, Plotkin LI, et al. Nongenetropic sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 2001;104:719–730. 45. Fukayama S, Tashjian AH Jr. Direct modulation of androgens of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. Endocrinol 1989;125: 1789–1794. 46. Pilbeam CC, Raisz LG. Effects of androgens on parathyroid hormone and interleukin-1-stimulated prostaglandin production in cultured neonatal mouse calvariae. J Bone Miner Res 1990; 5:1183–1188. 47. Bellido T, Jilka RL, Boyce BF, et al. Regulation of interleukin-6 osteoclastogenesis and bone mass by androgens. J Clin Invest 1995;95:1886–1895. 48. Purohit A, Flanagan AM, Reed MJ. Estrogen synthesis by osteoblast cell lines. Endocrinol 1992;131:2027–2029. 49. Bruch HR, Wolf L, Budde R, et al. Androstenedione metabolism in cultured human osteoblast-like cells. J Clin Endocrinol Metab 1992;75:101–105. 50. Janssen JM, Bland R, Hewison M, et al. Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function. J Cell Biochem 1999;75:528–537.
230 Kenny and Raisz 51. Morishima A, Grumbach MM, Simpson ER, et al. Aromatase deficiency in male and femal siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–3698. 52. Bilezikian JP, Morishima A, Bell J, Grumbach MM. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. N Eng J Med 1998;339:599–603. 53. Imperato-McGinley J. 5 Alpha-reductase-2 deficiency. Curr Ther Endocrinol Metab 1997;6:384–387. 54. Kasra M, Grynpas MD. The effects of androgens on the mechanical properties of primate bone. J Biomech Eng 1995;17:265–270. 55. Lundon K, Dumitriu M, Grynpas MD. Suprphysiologic levels of testosterone affect cancellous and cortical bone in the young female cynomolgus monkey. Calcif Tissue Int 1997;60:54–62. 56. Gunness M, Orwoll E. Early induction of alterations in cancellous and cortical bone histology after orchidectomy in mature rats. J Bone Miner Res 1995;10:1735–1744. 57. Vanderschueren D, Van Herck E, Suiker AM, et al. Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency. Endocrinol 1992;130:2906–2916. 58. Mason RA, Morris HA. Effects of dihydrotestosterone on bone biochemical markers in sham and oophorectomized rats. J Bone Miner Res 1997;12:1431–1437. 59. Lea CK, Flanagan AM. Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182, 780. J Endocrin 1999;160:111–117. 60. Vanderschueren D, Van Herck E,, Nijs J, et al. Aromatase inhibition impairs skeletal modeling an decreases bone mineral density in growing male rats. Endocrinol 1997;138:23201–23207. 61. Oz OK, Zerwekh JE, Fisher C, et al. Bone has a sexually dimorphic response to aromatase deficiency. J Bone Miner Res 2000;15:507–514. 62. Miyaura C, Toda K, Inada M, et al. Sex and age-related response to aromatase deficiency in bone. Biochem Biophys Res Commun 2001;280:1062–1068. 63. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994;331:1056–1061. 64. Marcus R, Leary D, Schneider DL, et al. The contribution of testosterone to skeletal development and maintenance lessons from the androgen insensitivity syndrome. J Clin Endocrinol Metab 2000;85:1032–1037. 65. Soule SG, Conway G, Prelevic GM, et al. Osteopenia as a feature of the androgen insensitivity syndrome. Clin Endocrinol 1995;43:671–675. 66. Mauras N, O’Brien KO, Oerter Klein K, Hayes V. Estrogen suppression in males: metabolic effects. J Clin Endocrinol Metab 2000;85:2370–2377. 67. Munoz-Torres M, Jodar E, Quesada M, Escobar-Jiminez F. Bone mass in androgen-insensitivity syndrome: response to hormonal replacement therapy. Calcif Tissue Int 1995;57:94–96. 68. Stepan IJ, Lachman M, Zverina J, et al. Castrated men exhibit bone loss: Effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 1989;69:523–527. 69. Finkelstein JS, Klibanski A, Neer RM, et al. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med 1987;106:354–361. 70. Finkelstein JS, Neer RM, Biller BM, et al. Osteopenia in men with a history of delayed puberty. N Engl J Med 1992;326:600–604. 71. Finklestein JS, Klibanski A, Neer RM. A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty. J Clin Endocrinol Metab 1996;81:1152–1155. 72. Finkelstein JS, Kilbanski A, Neer RM. Evaluation of lumber spine bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA) in 21 young men with histories of constitutionallydelayed puberty. J Clin Endocrinol Metab 1998;83:4280–4283. 73. Kiratli BJ, Srinivas S, Perkash I, Terris MK. Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer. Urology 2001;57:127–132. 74. Leder BZ, Smith MR, Fallon MA, et al. Effects of gonadal steroid suppression on skeletal sensitivity to parathyroid hormone in men. J Clin Endocrinol Metab 2001;86:511–516. 75. Foresta C, Ruzza G, Mioni R, et al.Osteoporosis and decline of gonadal function in the elderly male. Horm Res 1984;19:18–22. 76. Francis RM, Peacock M, Aaron JE, et al. Osteoporosis in hypogonadal men: Role of decreased plasma 1,25-dihydroxyvitamin D, calcium malabsorption, and low bone formation. Bone 1986;7:261–268. 77. Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992;75(4):1092–1098.
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CONTEMPORARY ENDOCRINOLOGY Androgen
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CONTEMPORARY ENDOCRINOLOGY P. Micha
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© 2003 Humana Press Inc. 999 River
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vi Preface We hope Androgens in Hea
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viii Contents 13 Androgens and Body
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x Contributors RICHARD S. LEGRO, MD
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2 Winters and Clark
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4 Winters and Clark chorionic gonad
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6 Winters and Clark LH REGULATION O
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8 Winters and Clark These enzymes a
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10 Winters and Clark -subunit mRNA
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12 Winters and Clark Fig. 3. A sche
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14 Winters and Clark Table 1 Factor
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16 Winters and Clark Table 2 Tissue
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18 Winters and Clark 11. Thomas JL,
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20 Winters and Clark 61. Dufau ML,
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22 Winters and Clark 112. Raivio T,
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24 Brown Fig. 1. Mechanism for andr
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26 Brown increase in intracellular
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28 Brown Fig. 2. Structural and fun
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30 Brown Fig. 3. Amino acid sequenc
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32 Brown tions to shuttle the AR th
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34 Brown Fig. 4. Amino acid primary
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36 Brown part of an inactive chroma
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38 Brown the external genitalia is
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40 Brown tors, as well as the trans
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42 Brown 49. Williams SP, Sigler PB
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44 Brown 100. Gregory CW, He B, Joh
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46 Plymate Table 1 Classification o
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48 Plymate In addition to the direc
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50 Plymate LABORATORY FINDINGS In p
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52 Plymate those manifesting as phe
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54 Plymate result in some improveme
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56 Plymate If both testosterone and
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58 Plymate Persistent Müllerian Du
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60 Plymate INFERTILITY RESULTING FR
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62 Plymate unaffected, contralatera
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64 Plymate SECONDARY HYPOGONADISM H
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66 Plymate Other syndromes manifest
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68 Plymate period after the burn. I
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70 Plymate These findings suggest t
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72 Plymate 49. Goebelsmann U, Horto
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74 Plymate 104. Yoshimoto Y, Moride
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76 Plymate
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78 Sutton, Amory, and Clark levels
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80 Sutton, Amory, and Clark cebo in
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82 Sutton, Amory, and Clark Finaste
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84 Sutton, Amory, and Clark through
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86 Sutton, Amory, and Clark 40. The
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88 Sutton, Amory, and Clark 88. Rob
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90 Lindzey and Korach Fig. 1. Cellu
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92 Lindzey and Korach estrogen sign
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94 Lindzey and Korach TESTIS AND DU
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96 Lindzey and Korach sufficient to
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98 Lindzey and Korach Seminal Vesic
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100 Lindzey and Korach 17. Krege JH
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102 Lindzey and Korach 68. Chang WY
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104 McPhaul on the Y chromosome det
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106 106 McPhaul
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108 McPhaul number of alleles, dele
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110 McPhaul The first mutation of t
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112 McPhaul gene. In vitro studies
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114 McPhaul risk of impaired sperma
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116 McPhaul carrying a single mutan
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118 McPhaul REFERENCES 1. Koopman P
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120 McPhaul 45. Weidemann W, Peters
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122 McPhaul 92. Koivisto P, Kononen
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124 Legro Fig. 1. The spectrum of p
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126 Legro Virilization presents wit
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128 Legro Fig. 3. The paradox of an
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130 Legro small high-density athero
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132 Legro Table 2 Syndromes or Dise
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134 Legro Insulin-Sensitizing Agent
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136 Legro is undetermined according
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138 Legro 39. Lee O, Farquhar C, To
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140 Legro
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142 Wang and Swerdloff PHARMACOLOGY
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144 Wang and Swerdloff The 17α-alk
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146 Wang and Swerdloff Table 2 Dose
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148 Wang and Swerdloff The steroid
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150 Wang and Swerdloff The inabilit
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152 Wang and Swerdloff 15. De Lorim
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154 Wang and Swerdloff
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156 Marcelli et al.
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158 Marcelli et al. Differentiated
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160 Marcelli et al. These coactivat
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162 Marcelli et al. tigators have e
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164 Marcelli et al. AR in Prostate
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166 Marcelli et al. Table 1 Androge
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168 Marcelli et al. A molecular exp
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170 Marcelli et al. The above data
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172 Marcelli et al. up to 9 yr late
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174 Marcelli et al. Three major pha
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176 Marcelli et al. vitro model of
Page 189 and 190: 178 Marcelli et al. yr, survival wa
Page 191 and 192: 180 Marcelli et al. 26. McKenna NJ,
Page 193 and 194: 182 Marcelli et al. 78. Isaacs J, C
Page 195 and 196: 184 Marcelli et al. 126. Watanabe M
Page 197 and 198: 186 Marcelli et al. 177. Kousteni S
Page 199 and 200: 188 Marcelli et al. 231. Colombel M
Page 201 and 202: 190 Marcelli et al.
Page 203 and 204: 192 Wu and von Eckardstein contrace
Page 205 and 206: 194 Wu and von Eckardstein beam com
Page 207 and 208: 196 Wu and von Eckardstein excess o
Page 209 and 210: 198 Wu and von Eckardstein Endogeno
Page 211 and 212: Table 3 Change in Lipids in Hypogon
Page 213 and 214: Table 3 (continued) ∆LDL ∆HDL
Page 215 and 216: 204 Wu and von Eckardstein THE HEMO
Page 217 and 218: 206 Wu and von Eckardstein In vivo
Page 219 and 220: 208 Wu and von Eckardstein (uptake
Page 221 and 222: 210 Wu and von Eckardstein 4. Bhasi
Page 223 and 224: 212 Wu and von Eckardstein 57. Barr
Page 225 and 226: 214 Wu and von Eckardstein 107. Fra
Page 227 and 228: 216 Wu and von Eckardstein 152. Zmu
Page 229 and 230: 218 Wu and von Eckardstein 201. Cho
Page 231 and 232: 220 Wu and von Eckardstein 250. Eic
Page 233 and 234: 222 Kenny and Raisz with a cartilag
Page 235 and 236: 224 Kenny and Raisz METABOLISM OF A
Page 237 and 238: 226 Kenny and Raisz The level of th
Page 239: 228 Kenny and Raisz REFERENCES 1. G
Page 243 and 244: 232 Kenny and Raisz 103. Snyder PJ,
Page 245 and 246: 234 Basaria and Dobs losses in wome
Page 247 and 248: 236 Basaria and Dobs 15 dialysis pa
Page 249 and 250: 238 Basaria and Dobs duced remissio
Page 251 and 252: 240 Basaria and Dobs hematocrit lev
Page 253 and 254: 242 Basaria and Dobs 40. Sanchez-Me
Page 255 and 256: 244 Katznelson in men with testoste
Page 257 and 258: 246 Katznelson Fig. 1. Body weight,
Page 259 and 260: 248 Katznelson change during treatm
Page 261 and 262: 250 Katznelson testosterone or free
Page 263 and 264: 252 Katznelson disproportionate dec
Page 265 and 266: 254 Katznelson have been additional
Page 267 and 268: 256 Katznelson 18. Marin P, Lonn L,
Page 269 and 270: 258 Katznelson 71. Davis SR, McClou
Page 271 and 272: 260 Bancroft Androgen Deficiency an
Page 273 and 274: 262 Bancroft studies had presented
Page 275 and 276: 264 Bancroft Bagatell et al. (36) g
Page 277 and 278: 266 Bancroft much larger group of a
Page 279 and 280: 268 Bancroft In a report of a serie
Page 281 and 282: 270 Bancroft onset was related to a
Page 283 and 284: 272 Bancroft Particularly confusing
Page 285 and 286: 274 Bancroft 4. Studies using place
Page 287 and 288: 276 Bancroft either E and T or plac
Page 289 and 290: 278 Bancroft cytotoxic therapy supp
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280 Bancroft Women with Endocrine A
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282 Bancroft in response to the fil
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284 Bancroft Men are much more awar
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286 Bancroft 22. Morales A, Johnsto
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288 Bancroft 78. Hyde JS, DeLamater
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290 Bancroft 129. Appelt H, Strauss
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292 Cherrier and Craft Fig. 1. Path
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294 Cherrier and Craft ment of the
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296 Cherrier and Craft information
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298 Cherrier and Craft Fig. 3. Wech
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300 Cherrier and Craft gen excess r
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302 Cherrier and Craft occurring wi
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304 Cherrier and Craft gesting that
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306 Cherrier and Craft 39. Gouchie
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308 Cherrier and Craft 94. Kelso WM
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310 Cherrier and Craft
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312 Matsumoto
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314 Matsumoto long-term benefits an
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316 Matsumoto manifestations (7). F
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318 Formulation Usual adult dosage
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320 Matsumoto Fig. 1. Mean serum T
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322 Matsumoto dosage is increased g
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324 Matsumoto Androgel 5 g (50 mg o
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326 Matsumoto gen receptor and tiss
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328 Matsumoto such as hepatic cirrh
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330 Matsumoto occasionally, more se
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332 Matsumoto 27. Bhasin S, Bremner
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334 Matsumoto 77. Dobs AS, Meikle A
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336 Richmond and Rogol PHYSIOLOGY O
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338 Richmond and Rogol activity (28
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340 Richmond and Rogol increase lin
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342 Richmond and Rogol curve, the h
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344 Richmond and Rogol Permanent hy
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346 Richmond and Rogol 46. Stanhope
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348 Tenover In aging men, the combi
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350 Tenover Table 1 Changes in Andr
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352 Tenover studies in which eugona
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354 Tenover Table 3 Testosterone Th
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356 Tenover Table 5 ART in Older Me
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358 Tenover be overcome with either
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360 Tenover Laboratory tests should
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362 Tenover 40. Kohrt WM, Malley MT
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364 Tenover 95. Mooradian AD, Morle
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366 Davis Table 1 Proposed Androgen
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368 Davis transdermal testosterone
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370 Davis increase in circulating t
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372 Davis (93). Most recently, Zhou
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374 Davis Table 4 Androgen Replacem
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376 Davis 8. Vierhapper H, Nowotny
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378 Davis 60. Simberg N, Titinen A,
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380 Davis
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382 Bhasin, Woodhouse, and Storer h
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384 Table 2 Effects of Testosterone
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386 Bhasin, Woodhouse, and Storer e
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388 Bhasin, Woodhouse, and Storer F
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390 Bhasin, Woodhouse, and Storer t
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Table 3 Effects of Testosterone Sup
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Table 4 Effects of Testosterone Sup
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396 Bhasin, Woodhouse, and Storer c
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398 Bhasin, Woodhouse, and Storer C
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400 Bhasin, Woodhouse, and Storer w
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402 Bhasin, Woodhouse, and Storer 4
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404 Bhasin, Woodhouse, and Storer
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406 Amory Fig. 1. The endocrinology
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408 Amory pregnancies fathered by t
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410 Amory antagonists can suppress
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412 Amory 100-mg doses of weekly TE
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414 Amory FUTURE DIRECTIONS Given t
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416 Amory 22. Oral contraception. I
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418 Amory
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420 Anawalt inadequate androgen eff
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422 Anawalt few specialty commercia
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424 Anawalt Fig. 1. (C) Secondary h
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426 Anawalt Fig. 2. Evaluation and
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428 Anawalt All men with secondary
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430 Anawalt anemia (38). With the a
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432 Anawalt osterone levels achieve
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434 Anawalt SIDE EFFECTS OF ANDROGE
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436 Anawalt 7. Rosner W. Errors in
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438 Anawalt 59. Mackey MA, Conway A
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440 Index polycystic ovaries, 131 A
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442 Index lipoid congenital adrenal
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444 Index women, 254 dihydrotestost
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446 Index Pituitary adenoma, male h
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448 Index lipoid congenital adrenal
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