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Horm Metab Res 2002; 34(5): 223-228
DOI: 10.1055/s-2002-32144
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Intrinsic Regional Differences in Androgen Receptors and Dihydrotestosterone Metabolism in Human Preadipocytes

J.  Joyner1 , L.  Hutley1 , D.  Cameron1
  • 1Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Wolloongabba, Queensland, Australia
Further Information

Publication History

16 October 2001

29 January 2002

Publication Date:
10 June 2002 (online)

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Abstract

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAs remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.

Key words

Adipose Tissue - Obesity - Androstanediol - Subcutaneous - Visceral

References

  • 1 Bosello O, Zamboni M. Visceral obesity and metabolic syndrome.  Obes Rev. 2000;  1 47-56
    CrossrefPubMedGoogle Scholar
  • 2 Tchernof A, Després J-P. Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women.  Horm Metab Res. 2000;  32 526-536
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Elbers J MH, Asscheman H, Seidell J C, Megens J AJ, Gooren L JG. Long-term testosterone administration increases visceral fat in female to male transexuals.  J Clin Endocrinol Metab. 1997;  82 2044-2047
    CrossrefPubMedGoogle Scholar
  • 4 Mårin P, Holmang S, Jönsson L, Sjöström L, Kvist H, Holm G, Lindstedt G, Björntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men.  Int J Obesity. 1992;  16 991-997
    PubMedGoogle Scholar
  • 5 Prins J B, O’Rahilly S. Regulation of adipose cell number in man.  Clin Sci. 1997;  92 3-11
    PubMedGoogle Scholar
  • 6 Miller L K, Kral J G, Strain G W, Zumoff B. Androgen binding to ammonium sulfate precipitates of human adipose tissue cytosols.  Steroids. 1990;  55 410-415
    CrossrefPubMedGoogle Scholar
  • 7 Dieudonné M N, Pecquery R, Boumediene A, Leneveu M C, Giudicelli Y. Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids.  Am J Physiol. 1998;  274 C1645-C1652
    PubMedGoogle Scholar
  • 8 Jaubert A-M, Pecquery R, Sichez I, Dieudonne M-N, Cloix J-F, Giudicelli Y. Androgen receptors in hamster white adipocytes and their precursor cells: regional variations and modulations by androgens.  Endocrine J. 1993;  1 535-540
    PubMedGoogle Scholar
  • 9 Roncari D AK. Hormonal influences on the replication and maturation of adipocyte precursors.  Int J Obesity. 1981;  5 547-552
    PubMedGoogle Scholar
  • 10 Anderson L A, McTernan P G, Barnett A H, Kumar S. The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: Influence of gender and site.  J Clin Endocrinol Metab. 2001;  86 5045-5051
    CrossrefPubMedGoogle Scholar
  • 11 Dieudonné M N, Pecquery R, Leneveu M C, Giudicelli Y. Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor gamma 2.  Endocrinology. 2000;  141 649-656
    CrossrefPubMedGoogle Scholar
  • 12 Joyner J M, Hutley L J, Cameron D P. Glucocorticoid receptors in human preadipocytes: regional and gender differences.  J Endocrinol. 2000;  166 145-152
    CrossrefPubMedGoogle Scholar
  • 13 Rodbell M. Metabolism of isolated fat cells.  J Biol Chem . 1964;  239 375-380
    PubMedGoogle Scholar
  • 14 Adams M, Montague C T, Prins J B, Holder J C, Smith S A, Sanders L, Sewter C P, Digby J E, Lazar M A, Chatterjee V KK, O’Rahilly S. Activators of PPARτ have depot-specific effects on human preadipocyte differentiation.  J Clin Invest. 1997;  100 3149-3153
    CrossrefPubMedGoogle Scholar
  • 15 Brown T R, Migeon C J. Cultured human skin fibroblasts: a model for the study of androgen action.  Mol Cell Biochem. 1981;  36 3-22
    PubMedGoogle Scholar
  • 16 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocynanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
    PubMedGoogle Scholar
  • 17 Iwai M, Kanzak H, Fujimoto M, Kojima K, Hatayama H, Inoue T, Higuchi T, Nakayama H, Mori K, Fujita J. Regulation of sex steroid receptor gene expression by progesterone and testosterone in cultured human endometrial stromal cells.  J Clin Endocrinol Metab. 1995;  80 450-454
    CrossrefPubMedGoogle Scholar
  • 18 Dibattista J A, Martel-Pelletier J, Antakly T, Tardif G, Cloutier J-M, Pelletier J-P. Reduced expression of glucocorticoid receptor levels in human osteoarthritic chondrocytes. Role in the suppression of metalloprotease synthesis.  J Clin Endocrinol Metab. 1993;  76 1128-1134
    CrossrefPubMedGoogle Scholar
  • 19 Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
    CrossrefPubMedGoogle Scholar
  • 20 Gower D B. Biosynthesis of androgens and other C19 steroids. In: Makin HLJ (ed) Biochemistry of Steroid Hormones. Oxford/Melbourne; Blackwell Scientific Publications 1984: 170-206
    Google Scholar
  • 21 Lippman M, Bolan G, Huff K. The effects of androgens and antiandrogens on homone-responsive human breast cancer in long-term tissue culture.  Cancer Res. 1976;  36 4610-4618
    PubMedGoogle Scholar
  • 22 Engel L W, Young N A, Tralka T S, Lippman M E, O'Brian S J, Joyce M J. Establishment and characterization of three new continuous cell lines derived from human breast carcinomas.  Cancer Res. 1978;  38 3352-3364
    PubMedGoogle Scholar
  • 23 Sultan C, Migeon B R, Rothwell S W, Maes M, Zerhouni N, Migeon C J. Androgen receptors and metabolism in cultured human fetal fibroblasts.  Pediatr Res. 1980;  14 67-69
    PubMedGoogle Scholar
  • 24 Pinsky L, Kaufman M, Straisfeld C, Shanfield B. Lack of difference in testosterone metabolism between cultured skin fibroblasts of human adult males and females.  J Clin Endocrinol Metab. 1974;  39 395-398
    PubMedGoogle Scholar
  • 25 Pedersen S B, Fuglsig S, Sjøgren P, Richelsen B. Identification of steroid receptors in human adipose tissue.  Eur J Clin Invest. 1996;  26 1051-1056
    CrossrefPubMedGoogle Scholar
  • 26 Ono K, Haji M, Nawata H, Maki T, Kato K-I, Ibayashi H. Age-related changes in glucocorticoid and androgen receptors of cultured human pubic skin fibroblasts.  Gerontology. 1988;  34 128-133
    PubMedGoogle Scholar
  • 27 McTernan P G, Anwar A, Eggo M C, Barnett A H, Stewart P M, Kumar S. Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue.  Int J Obes. 2000;  24 875-881
    CrossrefPubMedGoogle Scholar
  • 28 Pinsky L, Kaufman M, Gil-Esteban C, Sumbulian D. Regulation of the androgen receptor in human genital skin fibroblasts, with a review of sex steroid receptor regulation by homologous and heterologous steroids.  Can J Biochem Cell Biol. 1983;  61 770-778
    PubMedGoogle Scholar
  • 29 Kaufman M, Pinsky L, Hollander R, Bailey J D. Regulation of the androgen receptor by androgen in normal and androgen-resistant genital skin fibroblasts.  J Steroid Biochem. 1983;  18 383-390
    CrossrefPubMedGoogle Scholar
  • 30 Killinger D W, Perel E, Daniilescu D, Kharlip L, Lindsay W RN. The relationship between aromatase activity and body fat distribution.  Steroids. 1987;  50 61-72
    CrossrefPubMedGoogle Scholar
  • 31 Bujalska I, Kumar S, Stewart P M. Does central obesity reflect “Cushing’s disease of the omentum”?.  Lancet. 1997;  349 1210-1213
    CrossrefPubMedGoogle Scholar
  • 32 Nakano K, Fukabori Y, Itoh N, Lu W, Kan M, Mckeehan W L, Yamanaka H. Androgen-stimulated human prostatic epithelial growth mediated by stromal-derived fibroblastic growth factor-10.  Endocrine J. 1999;  46 405-413
    PubMedGoogle Scholar
  • 33 Joyner J M, Hutley L J, Cameron D P. Estrogen receptors in human preadipocytes.  Endocrine. 2001;  15 225-230
    CrossrefPubMedGoogle Scholar
  • 34 Simpson E, Rubin G, Clyne C, Robertson K, O’Donnell L, Jones M, Davis S. The role of local estrogen biosynthesis in males and females.  Trends Endocrinol Metab. 2000;  11 184-188
    PubMedGoogle Scholar
  • 35 Lawrence V J, Coppack S W. The endocrine function of the fat cell-regulation by the sympathetic nervous system.  Horm Metab Res . 2000;  32 453-467
    PubMedGoogle Scholar
  • 36 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease.  Horm Metab Res. 2000;  32 485-499
    Article in Thieme ConnectPubMedGoogle Scholar

Dr. J. Joyner

Department of Diabetes and Endocrinology · Princess Alexandra Hospital

Ipswich Road · Woolloongabba 4102 · Queensland · Australia ·

Phone: + 61 (7) 3240-2697

Fax: + 61 (7) 3240-2973 ·

Email: julie_joyner@health.qld.gov.au.

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