The mutual dependence between bone and gonads

Journal of Endocrinology

Volumn 213, Issue 2, 2012, Pages 107-114

  Karsenty, Gerard ^a  

^a Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ESTRADIOL; G PROTEIN COUPLED RECEPTOR; OSTEOCALCIN; TESTOSTERONE;

BONE; BONE GROWTH; BONE MASS; ESTRADIOL BLOOD LEVEL; GONAD; HORMONE ACTION; HUMAN; LEYDIG CELL; MALE FERTILITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SYMBIOSIS; TESTOSTERONE SYNTHESIS;

BONE AND BONES; BONE DEVELOPMENT; FEMALE; GONADAL STEROID HORMONES; GONADS; HUMANS; LEYDIG CELLS; MALE; OSTEOBLASTS; OSTEOCALCIN; RECEPTORS, G-PROTEIN-COUPLED; REPRODUCTION; TESTOSTERONE;

EID: 84862065611     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1530/JOE-11-0452     Document Type: Review

References (90)

1. Aonuma H, Miyakoshi N, Hongo M, Kasukawa Y & Shimada Y 2009 Low serum levels of undercarboxylated osteocalcin in postmenopausal osteoporotic women receiving an inhibitor of bone resorption. Tohoku Journal of Experimental Medicine 218 201-205.
2. Araujo AB, Travison TG, Leder BZ & McKinlay JB 2008 Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men. Journal of Clinical Endocrinology and Metabolism 93 2135-2141.
3. van den Beld AW, de Jong FH, Grobbee DE, Pols HA & Lamberts SW 2000 Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. Journal of Clinical Endocrinology and Metabolism 85 3276-3282.
4. Bertelloni S, Baroncelli GI, Battini R, Perri G & Saggese G 1995 Shortterm effect of testosterone treatment on reduced bone density in boys with constitutional delay of puberty. Journal of Bone and Mineral Research 10 1488-1495.
5. Bodine PV, Riggs BL & Spelsberg TC 1995 Regulation of c-fos expression and TGF-b production by gonadal and adrenal androgens in normal human osteoblastic cells. Journal of Steroid Biochemistry and Molecular Biology 52 149-158.
6. Bord S, Horner A, Beavan S & Compston J 2001 Estrogen receptors a and b are differentially expressed in developing human bone. Journal of Clinical Endocrinology and Metabolism 86 2309-2314.
7. Bouillon R, Bex M, Vanderschueren D & Boonen S 2004 Estrogens are essential for male pubertal periosteal bone expansion. Journal of Clinical Endocrinology and Metabolism 89 6025-6029.
8. Buchanan JR, Myers C, Lloyd T, Leuenberger P & Demers LM 1988 Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise. Journal of Bone and Mineral Research 3 673-680.
9. Callewaert F, Venken K, Ophoff J, De Gendt K, Torcasio A, van Lenthe GH, Van Oosterwyck H, Boonen S, Bouillon R, Verhoeven G et al. 2009 Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-a. FASEB Journal 23 232-240.
10. Callewaert F, Boonen S & Vanderschueren D 2010a Sex steroids and the male skeleton: a tale of two hormones. Trends in Endocrinology and Metabolism 21 89-95.
11. Callewaert F, Sinnesael M, Gielen E, Boonen S & Vanderschueren D 2010b Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1, and mechanical loading. Journal of Endocrinology 207 127-134.
12. Callewaert F, Venken K, Kopchick JJ, Torcasio A, van Lenthe GH, Boonen S & Vanderschueren D 2010c Sexual dimorphism in cortical bone size and strength but not density is determined by independent and time-specific actions of sex steroids and IGF-1: evidence from pubertal mouse models. Journal of Bone and Mineral Research 25 617-626.
13. Clarke BL & Khosla S 2010 Physiology of bone loss. Radiologic Clinics of North America 48 483-495.
14. Couse JF & Korach KS 1999 Estrogen receptor null mice: what have we learned and where will they lead us? Endocrine Reviews 20 358-417
15. Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ & Korach KS 1999 Postnatal sex reversal of the ovaries in mice lacking estrogen receptors α and β. Science 286 2328-2331.
16. Fernandez-Real JM, Izquierdo M, Ortega F, Gorostiaga E, Gomez-Ambrosi J, Moreno-Navarrete JM, Fruhbeck G, Martinez C, Idoate F, Salvador J et al. 2009 The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. Journal of Clinical Endocrinology and Metabolism 94 237-245.
17. Ferron M, Hinoi E, Karsenty G & Ducy P 2008 Osteocalcin differentially regulates b cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. PNAS 105 5266-5270.
18. FerronM, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P & Karsenty G 2010 Insulin signaling in osteoblasts integrates bone remodeling and energymetabolism. Cell 142 296-308.
19. Finkelstein JS, Klibanski A & Neer RM 1996 A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty. Journal of Clinical Endocrinology and Metabolism 81 1152-1155.
20. Fulzele K, RiddleRC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Bruning JC et al. 2010 Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142 309-319.
21. Garnero P, Sornay-Rendu E, Chapuy MC & Delmas PD 1996 Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. Journal of Bone and Mineral Research 11 337-349.
22. Gill RK, Turner RT, Wronski TJ & Bell NH 1998 Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor b in rat bone, and reduction is prevented by testosterone. Endocrinology 139 546-550.
23. Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Myers MG Jr, Chua SC Jr, Kim JK, Kaestner KH & Karsenty G 2008 The sympathetic tone mediates leptin's inhibition of insulin secretion bymodulating osteocalcin bioactivity. Journal of Cell Biology 183 1235-1242.
24. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR & Boyce BF 1996 Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-b. Nature Medicine 2 1132-1136.
25. Hwang YC, Jeong IK, Ahn KJ & Chung HY 2009 The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced b-cell function in middle-aged male subjects. Diabetes/Metabolism Research and Reviews 25 768-772.
26. Im JA, Yu BP, Jeon JY & Kim SH 2008 Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clinica Chimica Acta 396 66-69.
27. Imai Y, Youn MY, Kondoh S, Nakamura T, Kouzmenko A, Matsumoto T, Takada I, Takaoka K & Kato S 2009 Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts. Annals of the New York Academy of Sciences 1173 (Suppl 1) E31-E39.
28. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H &Manolagas SC 1992 Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257 88-91.
29. Jimi E, Ikebe T, Takahashi N, Hirata M, Suda T & Koga T 1996 Interleukin-1α activates an NF-kappaB-like factor in osteoclast-like cells. Journal of Biological Chemistry 271 4605-4608.
30. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S & Sugimoto T 2009 Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 94 45-49.
31. Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT & Baylink DJ 1989 Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 124 1576-1578.
32. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ & Klibanski A 1996 Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. Journal of Clinical Endocrinology and Metabolism 81 4358-4365.
33. Kaufman JM & Vermeulen A 2005 The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocrine Reviews 26 833-876.
34. Kelly PJ, Twomey L, Sambrook PN & Eisman JA 1990 Sex differences in peak adult bone mineral density. Journal of Bone and Mineral Research 5 1169-1175.
35. Khosla S 2010 Update in male osteoporosis. Journal of Clinical Endocrinology and Metabolism 95 3-10.
36. Khosla S 2010 Update on estrogens and the skeleton. Journal of Clinical Endocrinology and Metabolism 95 3569-3577.
37. Khosla S & Riggs BL 2005 Pathophysiology of age-related bone loss and osteoporosis. Endocrinology and Metabolism Clinics of North America 34 1015-1030, xi.
38. Khosla S, Melton LJ III, Atkinson EJ & O'Fallon WM 2001 Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. Journal of Clinical Endocrinology and Metabolism 86 3555-3561.
39. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U & Mellstrom D 2009 Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. Journal of Bone and Mineral Research 24 785-791.
40. Kirmani S, Christen D, van Lenthe GH, Fischer PR, Bouxsein ML, McCready LK, Melton LJ III, Riggs BL, Amin S, Muller R et al. 2009 Bone structure at the distal radius during adolescent growth. Journal of Bone and Mineral Research 24 1033-1042.
41. Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS et al. 2001 Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104 719-730.
42. Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA, Plotkin L, Fu Q, Mancino AT, Wen Y et al. 2002 Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 298 843-846.
43. Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP & Brown M 2008 Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. EMBO Journal 27 535-545.
44. Kuang D, Yao Y, Lam J, Tsushima RG & Hampson DR 2005 Cloning and characterization of a family C orphan G-protein coupled receptor. Journal of Neurochemistry 93 383-391.
45. Leder BZ, Rohrer JL, Rubin SD, Gallo J & Longcope C 2004 Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. Journal of Clinical Endocrinology and Metabolism 89 1174-1180.
46. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY et al. 2007 Endocrine regulation of energy metabolism by the skeleton. Cell 130 456-469.
47. Levinger I, Zebaze R, Jerums G, Hare DL, Selig S & Seeman E 2011 The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporosis International 22 1621-1626.
48. Lindberg MK, Alatalo SL, Halleen JM, Mohan S, Gustafsson JA & Ohlsson C 2001 Estrogen receptor specificity in the regulation of the skeleton in female mice. Journal of Endocrinology 171 229-236.
49. Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB & Clarke AC 1976 Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1 1038-1041.
50. Lindsay R, Hart DM, Forrest C & Baird C 1980 Prevention of spinal osteoporosis in oophorectomised women. Lancet 2 1151-1154.
51. Lupu F, Terwilliger JD, Lee K, Segre GV & Efstratiadis A 2001 Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Developmental Biology 229 141-162.
52. Manolagas SC, Kousteni S & Jilka RL 2002 Sex steroids and bone. Recent Progress in Hormone Research 57 385-409.
53. Mellstrom D, JohnellO, LjunggrenO, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E & Ohlsson C 2006 Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. Journal of Bone and Mineral Research 21 529-535.
54. Michael H, Harkonen PL, Vaananen HK & Hentunen TA 2005 Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. Journal of Bone and Mineral Research 20 2224-2232.
55. Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y et al. 2007 Estrogen prevents bone loss via estrogen receptor a and induction of Fas ligand in osteoclasts. Cell 130 811-823.
56. Noble B, Routledge J, Stevens H, Hughes I & Jacobson W 1999 Androgen receptors in bone-forming tissue. Hormone Research 51 31-36.
57. Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P et al. 2011 Endocrine regulation of male fertility by the skeleton. Cell 144 796-809.
58. Oz OK, Zerwekh JE, Fisher C, Graves K, Nanu L, Millsaps R & Simpson ER 2000 Bone has a sexually dimorphic response to aromatase deficiency. Journal of Bone and Mineral Research 15 507-514.
59. Pacifici R 1996 Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. Journal of Bone and Mineral Research 11 1043-1051.
60. Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, Fontilla-Poole M, Mays RW, Brunden KR, Harrington JJ et al. 2005 Identification of a novel extracellular cation-sensing G-protein-coupled receptor. Journal of Biological Chemistry 280 40201-40209.
61. Pi M, Chen L, Huang MZ, ZhuW, Ringhofer B, Luo J, Christenson L, Li B, Zhang J, Jackson PD et al. 2008 GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS ONE 3 e3858.
62. Pi M, Zhang L, Lei SF, Huang MZ, Zhu W, Zhang J, Shen H, Deng HW & Quarles LD 2010 Impaired osteoblast function in GPRC6A null mice. Journal of Bone and Mineral Research 25 1092-1102.
63. Pi M, Wu Y & Quarles LD 2011 GPRC6A mediates responses to osteocalcin in b-cells in vitro and pancreas in vivo. Journal of Bone and Mineral Research 26 1680-1683.
64. Pincus G 1962 Reproduction. Annual Review of Physiology 24 57-84.
65. Pittas AG, Harris SS, Eliades M, Stark P & Dawson-Hughes B 2009 Association between serum osteocalcin and markers of metabolic phenotype. Journal of Clinical Endocrinology and Metabolism 94 827-832.
66. Rached MT, Kode A, Xu L, Yoshikawa Y, Paik JH, Depinho RA & Kousteni S 2010 FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. Cell Metabolism 11 147-160.
67. Riggs BL, O'Fallon WM, Muhs J, O'Connor MK, Kumar R &Melton LJ III 1998 Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. Journal of Bone and Mineral Research 13 168-174.
68. Riggs BL, Khosla S & Melton LJ III 2002 Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviews 23 279-302.
69. Rochira V, Zirilli L, Madeo B, Aranda C, Caffagni G, Fabre B, Montangero VE, Roldan EJ, Maffei L & Carani C 2007 Skeletal effects of long-term estrogen and testosterone replacement treatment in a man with congenital aromatase deficiency: evidences of a priming effect of estrogen for sex steroids action on bone. Bone 40 1662-1668.
70. Schnorr JA, Bray MJ & Veldhuis JD 2001 Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men. Journal of Clinical Endocrinology and Metabolism 86 2600-2606.
71. Seeman E 2001 Clinical review 137: sexual dimorphism in skeletal size, density, and strength. Journal of Clinical Endocrinology and Metabolism 86 4576-4584.
72. Stepan JJ, Lachman M, Zverina J, Pacovsky V & Baylink DJ 1989 Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. Journal of Clinical Endocrinology and Metabolism 69 523-527.
73. Stevenson JC, Cust MP, Gangar KF, Hillard TC, Lees B & Whitehead MI 1990 Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 336 265-269.
74. Tau KR, Hefferan TE, Waters KM, Robinson JA, Subramaniam M, Riggs BL & Spelsberg TC 1998 Estrogen regulation of a transforming growth factor-b inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts. Endocrinology 139 1346-1353.
75. T'Sjoen GG, Giagulli VA, Delva H, Crabbe P, De Bacquer D & Kaufman JM 2005 Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition. Journal of Clinical Endocrinology and Metabolism 90 5717-5722.
76. Vandenput L & Ohlsson C 2009 Estrogens as regulators of bone health in men. Nature Reviews. Endocrinology 5 437-443.
77. Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R & Ohlsson C 2004 Androgens and bone. Endocrine Reviews 25 389-425.
78. Venken K, Schuit F, Van Lommel L, Tsukamoto K, Kopchick JJ, Coschigano K, Ohlsson C, Moverare S, Boonen S, Bouillon R et al. 2005 Growth without growth hormone receptor: estradiol is a major growth hormoneindependent regulator of hepatic IGF-I synthesis. Journal of Bone and Mineral Research 20 2138-2149.
79. Venken K, De Gendt K, Boonen S, Ophoff J, Bouillon R, Swinnen JV, Verhoeven G & Vanderschueren D 2006 Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. Journal of Bone and Mineral Research 21 576-585.
80. Venken K, Callewaert F, Boonen S & Vanderschueren D 2008 Sex hormones, their receptors and bone health. Osteoporosis International 19 1517-1525.
81. Vidal O, Kindblom LG & Ohlsson C 1999 Expression and localization of estrogen receptor-b in murine and human bone. Journal of Bone and Mineral Research 14 923-929.
82. Vidal O, Lindberg MK, Hollberg K, Baylink DJ, Andersson G, Lubahn DB, Mohan S, Gustafsson JA & Ohlsson C 2000 Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. PNAS 97 5474-5479.
83. Wei S, Jones G, Thomson R, Otahal P, Dwyer T & Venn A 2010 Menstrual irregularity and bone mass in premenopausal women: cross-sectional associations with testosterone and SHBG. BMC Musculoskeletal Disorders 11 288.
84. Wellendorph P & Brauner-Osborne H 2004 Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene 335 37-46.
85. Wellendorph P, Johansen LD, Jensen AA, Casanova E, Gassmann M, Deprez P, Clement-Lacroix P, Bettler B & Brauner-Osborne H 2009 No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. Journal of Molecular Endocrinology 42 215-223.
86. Winhofer Y, Handisurya A, Tura A, Bittighofer C, Klein K, Schneider B, Bieglmayer C, Wagner OF, Pacini G, Luger A et al. 2010 Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 33 139-143.
87. Xing L & Boyce BF 2005 Regulation of apoptosis in osteoclasts and osteoblastic cells. Biochemical and Biophysical Research Communications 328 709-720.
88. Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP & Norman PE 2010 Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. European Journal of Endocrinology 163 265-272.
89. Yoshikawa Y, Kode A, Xu L, Mosialou I, Silva BC, Ferron M, Clemens TL, Economides AN & Kousteni S 2011 Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism. Journal of Bone and Mineral Research 26 2012-2025.
90. Zborowski JV, Cauley JA, Talbott EO, Guzick DS & Winters SJ 2000 Clinical review 116: bone mineral density, androgens, and the polycystic ovary: the complex and controversial issue of androgenic influence in female bone. Journal of Clinical Endocrinology and Metabolism 85 3496-3506.