Abstract
Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 ± 5.1 years, mean body mass index (BMI) 24.5 ± 5 kg/m2], and thirty respective controls were analyzed for the number of GR sites per cell (B max), apparent equilibrium dissociation constant (K d), and binding potency (GR potency). A strong association between B max and K d (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K d were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.
Similar content being viewed by others
References
S. Franks, N. Engl. J. Med. 333, 853–861 (1995)
E. Carmina, R.A. Lobo, J. Clin. Endocrinol. Metab. 84, 1897–1899 (1999)
R. Azziz, K.S. Woods, R. Reyna, T.J. Key, E.S. Knochenhauer, B.O. Yildiz, J. Clin. Endocrinol. Metab. 89, 2745–2749 (2004)
T.F. Gallagher, A. Kappas, L. Hellman, M.B. Lipsett, O.H. Pearson, C.D. West, J. Clin. Invest. 37, 794–799 (1958)
E. Steinberger, K.D. Smith, L.J. Rodriguez-Rigau, J. Clin. Endocrinol. Metab. 59, 471–477 (1984)
C. Moran, E. Knochenhauer, L.R. Boots, R. Azziz, Fertil. Steril. 71, 671–674 (1999)
E. Diamanti-Kandarakis, Expert Rev. Mol. Med. 10, e3 (2008)
P.M. Stewart, C.H. Shackleton, G.H. Beastall, C.R. Edwards, Lancet 335, 431–433 (1990)
A. Gambineri, V. Vicennati, S. Genghini, F. Tomassoni, U. Pagotto, R. Pasquali, B.R. Walker, J. Clin. Endocrinol. Metab. 91, 2295–2302 (2006)
D. Ehrmann, R. Barnes, R. Rosenfield, M. Cavaghan, J. Imperial, Diabetes Care 22, 141–146 (1999)
R.S. Legro, A.R. Kunselman, A. Dunaif, Am. J. Med. 111, 607–613 (2001)
D. Macut, S. Damjanovic, D. Panidis, N. Spanos, B. Glisic, M. Petakov, D. Rousso, A. Kourtis, J. Bjekic, N. Milic, Eur. J. Endocrinol. 155, 131–136 (2006)
D. Macut, D. Panidis, B. Glisic, N. Spanos, M. Petakov, J. Bjekic, O. Stanojlovic, D. Rousso, A. Kourtis, I. Bozic, S. Damjanovic, Can. J. Physiol. Pharmacol. 86, 199–204 (2008)
G. Arnaldi, A. Angeli, A.B. Atkinson, X. Bertagna, F. Cavagnini, G.P. Chrousos, G.A. Fava, J.W. Findling, R.C. Gaillard, A.B. Grossman, B. Kola, A. Lacroix, T. Mancini, F. Mantero, J. Newell-Price, L.K. Nieman, N. Sonino, M.L. Vance, A. Giustina, M. Boscaro, J. Clin. Endocrinol. Metab. 88, 5593–5602 (2003)
R.A. Covar, D.Y. Leung, D. McCormick, J. Steelman, P. Zeitler, J.D. Spahn, J. Allergy Clin. Immunol. 106, 651–659 (2000)
B.R. Walker, D.I.W. Phillips, J.P. Noon, M. Panarelli, R. Andrew, H.V. Edwards, D.W. Holton, J.R. Seckl, D.J. Webb, G.C. Watt, Hypertension 31, 891–895 (1998)
Yu.A. Shakhov, I.E. Petrichenko, N.V. Chepurnenko, N.V. Perova, R.G. Oganov, Biochem. Int. 18, 913–922 (1989)
R. Kumar, E.B. Thompson, J. Steroid Biochem. Mol. Biol. 94, 383–394 (2005)
X.K. Zhang, J.M. Dong, J.F. Chiu, J. Biol. Chem. 266, 8248–8254 (1991)
A. Ray, K.E. Prefontaine, Proc. Natl Acad. Sci. USA 91, 752–756 (1994)
Y. Tang, A. Lu, B.J. Aronow, F.R. Sharp, Ann. Neurol. 50, 699–707 (2001)
I. Elakovic, T. Perisic, M. Cankovic-Kadijevic, G. Matic, Cell Biochem. Funct. 25, 427–431 (2007)
M. Guven, O. Acbay, G. Sultuybek, Int. J. Gynaecol. Obstet. 63, 33–37 (1998)
T.F. Szuran, V. Pliška, J. Pokorny, H. Welzl, Physiol. Behav. 71, 353–362 (2000)
T. Tsilchorozidou, J.W. Honour, G.S. Conway, J. Clin. Endocrinol. Metab. 88, 5907–5913 (2003)
M. Fassnacht, N. Schlenz, S.B. Schneider, S.A. Wudy, B. Allolio, W. Arlt, J. Clin. Endocrinol. Metab. 88, 2760–2766 (2003)
K. Junker, J. Clin. Endocrinol. Metab. 57, 506–512 (1983)
T. Hirotoshi, H. Akama, Y. Ichikawa, M. Homma, H. Oshima, Clin. Chem. 37, 1715–1719 (1991)
F. Then-Bergh, A. Grasser, C. Trenkwalder, H. Backmund, F. Holsober, R. Rupprecht, J. Neurol. 246, 292–298 (1999)
M.M. Brentani, P.E. Marchiori, V.R. Martins, Acta Neurol. Scand. 72, 188–192 (1985)
T. Shimada, N. Hiwatashi, H. Yamayaki, Y. Kinouchi, T. Toyota, Dis. Colon Rectum 40(10 Suppl), S54–S58 (1997)
T. Hirano, A. Horigome, K. Oka, H. Takeuchi, M. Yoshida, E. Sakurai, K. Kozaki, N. Matsuno, T. Nagao, M. Kozaki, Immunopharmacology 36, 57–67 (1997)
S. Sanden, R. Tripmacher, R. Weltrich, W. Rohde, F. Hiepe, G.R. Burmester, F. Buttgereit, J. Rheumatol. 27, 1265–1270 (2000)
N.A. Huizenga, J.W. Koper, P. De Lange, H.A. Pols, R.P. Stolk, H. Burger, D.E. Grobbee, A.O. Brinkmann, F.H. De Jong, S.W. Lamberts, J. Clin. Endocrinol. Metab. 83, 144–151 (1998)
E.F. Van Rossum, S.W. Lamberts, Recent Prog. Horm. Res. 59, 333–357 (2004)
A.M. Di Blasio, E.F. van Rossum, S. Maestrini, M.E. Berselli, M. Tagliaferri, F. Podesta, J.W. Koper, A. Luizzi, S.W. Lamberts, Clin. Endocrinol. 59, 68–74 (2003)
S.M. Haffner, P. Karhapää, L. Mykkänen, M. Laakso, Diabetes 43, 212–219 (1994)
S. Saponaro, V. Guarnieri, G.P. Pescarmona, F. Silvagno, J. Steroid Biochem. Mol. Biol. 103, 129–136 (2007)
The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Fertil. Steril. 81, 19–25 (2004)
D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Diabetologia 28, 412–419 (1985)
W.T. Friedewald, R.I. Levy, D.S. Fredrickson, Clin. Chem. 18, 499–502 (1972)
R.S. Mathur, L.O. Moody, S. Landgrebbe, H.O. Williamson, Fertil. Steril. 35, 29–37 (1981)
Acknowledgments
This work was supported by the Ministry of Science of Serbia (Grant number 143003).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Macut, D., Vojnović Milutinović, D., Božić, I. et al. Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome. Endocr 37, 129–134 (2010). https://doi.org/10.1007/s12020-009-9277-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-009-9277-9