Androgens in Health and Disease.pdf - E Library

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205 Table 4 Effects of Testosterone on Vasoreactivity Study (ref.) Species Artery Study type Dose a Role of endothelium Vasodilation McCrohon et al. 1997 (197) Human (M-to-F transsexual) Brachial Case control 0 Dependent Increased Herman et al. 1997 (196) Human (M castrated) Brachial Case control 0 Dependent Increased New et al. 1997 (198) Human (F-to-M transsexual) Brachial Case control nmol Dependent and independent Decreased McCredie et al. 1998 (195) Human (F-to-M transsexual) Brachial Case control nmol Dependent and independent Decreased Webb et al. 1999 (16) Human (M) Coronary Intervention nmol Independent Increased Rosano et al. 1999 (17) Human (M) Coronary Intervention µmol ? Increased nmol No effect Ong et al. 2000 (199) Human (M) Brachial Intervention µmol Dependent Increased nmol No effect Warboys et al. 2001 (200) Human (F) Brachial Intervention nmol Dependent and independent Increased Adams et al. 1995 (51) Monkey (F) Coronary In vivo nmol Dependent Increased Chou et al. 1996 (201) Dog (M and F) Coronary In vivo µmol Dependent Increased Farhat et al. 1995 (203) Pig (M and F) Coronary Ex vivo µmol Dependent and independent Increased Quan et al. 1999 (206) Pig (M and F) Coronary Ex vivo µmol Independent Increased Teoh et al. 2000 (205) nmol Decreased Yue et al. 1995 (204) Rabbit (M and F) Coronary Ex vivo µmol Dependent and independent Increased Ceballos et al. 1999 (207) Rat Coronary Ex vivo nmol Dependent Decreased Costarella et al. 1996 (202) Rat (M) Aorta Ex vivo µmol Dependent and independent Increased Hutchison et al. 1997 (208) Rabbit Aorta Ex vivo nmol Dependent Decreased Geary et al. 2000 (209) Rat (M) Cerebral Ex vivo µmol Dependent Increased Note: M, male; F, female. a Refers to change in serum levels: 0, castration; nmol, nanomolar; µmol, micromolar. Chapter 10/Androgens and Coronary Artery Disease 205
206 Wu and von Eckardstein In vivo studies in monkeys and dogs of both sexes as well as most in vitro studies with animal vessels suggest that T exerts beneficial effects on vascular reactivity (51,201) (see Table 4). In vitro studies with isolated rings of coronary arteries and/or aortas from rats, rabbits, and pigs consistently found that T improved both endothelium-dependent and/or endothelium-independent vascular responsiveness (202–209) (see Table 4). Again, all of these studies employed supraphysiological to pharmacological doses of T, whereas physiological nanomolar dosages tended to inhibit vasodilatation (205–208). The cellular and molecular mechanisms by which T regulates vascular tone are not well understood. Evidence for and against endothelium-dependent or endotheliumindependent mechanisms are summarized in Table 4. In vitro expression of nitric oxide synthase in human aortic endothelial cells was stimulated by estradiol but not by T (210). T increased the response of coronary arteries to prostaglandin-F2α (203,211) whereas DHT increased the density of thromboxane receptors in smooth muscle cells (212). However, pretreatment with the prostaglandin synthase inhibitor indomethacin had no effect on T-induced vasodilation; therefore the role of eicosanoids in the vascular actions of T is controversial (201,204,205). Conversion to estradiol is not required because neither aromatase inhibitor nor the estrogen-receptor antagonist prevented the T-induced vasodilation (201,204). Two observations also indicate that T, especially in supraphysiological doses, modulates vascular tone via nongenomic mechanisms. First, the androgen receptor antagonists flutamide and cyproterone acetate did not inhibit the effects of T on rabbit or pig coronary arteries (204,205). Second, barium chloride attenuated the T-induced vasorelaxation of rabbit aortas and coronary arteries, indicating that T modulates the opening of potassium channels in vascular smooth muscle cells (204). In summary, T modulates vasoreactivity by both endothelium-dependent and endothelium-independent mechanisms, as well as by genomic and nongenomic modes of action. Physiological concentrations of T appear to inhibit vasodilatation by activation of the androgen receptor. In contrast, supraphysiological doses of testosterone can augment arterial vasodilatation through nongenomic actions. Effects of T on Macrophage Functions Increased uptake of oxidatively modified lipoproteins via type A scavenger receptors leads to the intracellular accumulation of cholesteryl esters in macrophages and thereby to foam cell formation (213–216). T increases the oxidation of LDL by placental macrophages in vitro (217). Dihydrotestosterone dose-dependently stimulates the uptake of acetylated LDL by scavenger receptor type A and intracellular cholesteryl ester accumulation in macrophages of male but not female donors (218). The effect was blocked by the androgen receptor antagonist hydroxyflutamide (218). Nonhepatic and nonsteroidogenic cells such as macrophages cannot metabolize cholesterol and can only dispose of excess cholesterol by secretion. Cholesterol efflux from cells is therefore central to the regulation of the cellular cholesterol homeostasis. To date, two plasma membrane proteins are known to facilitate active cholesterol efflux (see Fig. 1). Interaction of the scavenger receptor B1 with mature lipid-containing HDL facilitates cholesterol efflux by reorganizing the distribution of cholesterol within the plasma membrane. The ATP-binding cassette transporter (ABC) A1 mediates phospholipid and cholesterol efflux to extracellular lipid-free apolipoproteins by translocating these lipids from intracellular compartments to the plasma membrane and/or by forming a pore within the plasma membrane, through which the lipids are secreted (177).
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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
Page 165 and 166: 154 Wang and Swerdloff
Page 167 and 168: 156 Marcelli et al.
Page 169 and 170: 158 Marcelli et al. Differentiated
Page 171 and 172: 160 Marcelli et al. These coactivat
Page 173 and 174: 162 Marcelli et al. tigators have e
Page 175 and 176: 164 Marcelli et al. AR in Prostate
Page 177 and 178: 166 Marcelli et al. Table 1 Androge
Page 179 and 180: 168 Marcelli et al. A molecular exp
Page 181 and 182: 170 Marcelli et al. The above data
Page 183 and 184: 172 Marcelli et al. up to 9 yr late
Page 185 and 186: 174 Marcelli et al. Three major pha
Page 187 and 188: 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: 204 Wu and von Eckardstein THE HEMO
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 and 240: 228 Kenny and Raisz REFERENCES 1. G
Page 241 and 242: 230 Kenny and Raisz 51. Morishima A
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
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256 Katznelson 18. Marin P, Lonn L,
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258 Katznelson 71. Davis SR, McClou
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260 Bancroft Androgen Deficiency an
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262 Bancroft studies had presented
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264 Bancroft Bagatell et al. (36) g
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266 Bancroft much larger group of a
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268 Bancroft In a report of a serie
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270 Bancroft onset was related to a
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272 Bancroft Particularly confusing
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274 Bancroft 4. Studies using place
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276 Bancroft either E and T or plac
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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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