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The steroid RU486 induces UCP1 expression in brown adipocytes

  • Cell and Molecular Physiology
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Abstract

RU486 (mifepristone), a potent antagonist at progesterone and glucocorticoid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancies, the potential development of oral contraceptives, treatment of certain cancers and other activities. Potentially, it could also play a role in obesity control, although the few studies that have addressed this aspect have focused mainly on its central and anti-glucocorticoid effects. We have shown previously that it could have a direct effect on brown adipocytes in culture when administered together with progesterone. The aim of the present work was to analyse the effects of RU486 on the expression of uncoupling proteins (UCPs) in brown adipocytes. In culture-grown, differentiated brown adipocytes, placed in a serum-free medium to exclude the presence of progesterone or glucocorticoids, RU486 stimulated UCP1 expression at both the mRNA and protein levels. These effects could be mediated by PR, GR or other unknown mechanisms but do not seem to be due to its anti-progestin or anti-glucocorticoid actions. The results suggest that the steroid RU486 has a direct action on adipocytes which could be useful for stimulating non-shivering BAT thermogenesis and therefore is of interest in obesity studies.

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References

  1. Behl C, Trapp T, Skutella T, Holsboer F (1997) Protection against oxidative stress-induced neuronal cell death—a novel role for RU486. Eur J Neurosci 9:912–920

    CAS  PubMed  Google Scholar 

  2. Clapham JC, Turner NC (1997) Effects of the glucocorticoid II receptor antagonist mifepristone on hypertension in the obese Zucker rat. J Pharmacol Exp Ther 282:1503–1508

    CAS  PubMed  Google Scholar 

  3. Croxatto HB (2003) Mifepristone for luteal phase contraception. Contraception 68:483–488

    Article  CAS  PubMed  Google Scholar 

  4. Gettys TW, Watson PM, Taylor IL, Collins S (1997) RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient beta-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice. Int J Obes Relat Metab Disord 21:865–873

    Article  CAS  PubMed  Google Scholar 

  5. Ghoumari AM, Dusart I, El-Etr M, Tronche F, Sotelo C, Schumacher M, Baulieu EE (2003) Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum. Proc Natl Acad Sci USA 100:7953–7958

    Article  CAS  PubMed  Google Scholar 

  6. Hardwick AJ, Linton EA, Rothwell NJ (1989) Thermogenic effects of the antiglucocorticoid RU-486 in the rat: involvement of corticotropin-releasing factor and sympathetic activation of brown adipose tissue. Endocrinology 124:1684–1688

    CAS  PubMed  Google Scholar 

  7. Herron D, Rehnmark S, Nechad M, Loncar D, Cannon B, Nedergaard J (1990) Norepinephrine-induced synthesis of the uncoupling protein thermogenin (UCP) and its mitochondrial targeting in brown adipocytes differentiated in culture. FEBS Lett 268:296–300

    Article  CAS  PubMed  Google Scholar 

  8. Jacobsson A, Stadler U, Glotzer MA, Kozak LP (1985) Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem 260:16250–16254

    CAS  PubMed  Google Scholar 

  9. Jacobsson A, Cannon B, Nedergaard J (1987) Physiological activation of brown adipose tissue destabilizes thermogenin mRNA. FEBS Lett 224:353–356

    Article  CAS  PubMed  Google Scholar 

  10. Kramlik SK, Altemus M, Castonguay TW (1993) The effects of the acute administration of RU 486 on dietary fat preference in fasted lean and obese men. Physiol Behav 54:717–724

    Article  CAS  PubMed  Google Scholar 

  11. Langley SC, York DA (1990) Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats. Am J Physiol 259:R539–R544

    CAS  PubMed  Google Scholar 

  12. Mahajan DK, London SN (1997) Mifepristone (RU486): a review. Fertil Steril 68:967–976

    Article  CAS  PubMed  Google Scholar 

  13. Moriscot A, Rabelo R, Bianco AC (1993) Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue. Am J Physiol 265:E81–E87

    CAS  PubMed  Google Scholar 

  14. Okada S, York DA, Bray GA (1992) Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity. Am J Physiol 262:R1106–R1110

    CAS  PubMed  Google Scholar 

  15. Palou A, Picó C, Bonet ML, Oliver P (1998) The uncoupling protein, thermogenin. Int J Biochem Cell Biol 30:7–11

    Article  CAS  PubMed  Google Scholar 

  16. Parthasarathy S, Morales AJ, Murphy AA (1994) Antioxidant: a new role for RU-486 and related compounds. J Clin Invest 94:1990–1995

    CAS  PubMed  Google Scholar 

  17. Puigserver P, Llado I, Palou A, Gianotti M (1991) Evidence for masking of brown adipose tissue mitochondrial GDP-binding sites in response to fasting in rats made obese by dietary manipulation. Effects of reversion to standard diet. Biochem J 279:575–579

    CAS  PubMed  Google Scholar 

  18. Rodriguez AM, Palou A (2004) Uncoupling proteins: gender-dependence and their relation to body weight control. Int J Obes Relat Metab Disord 28:327–329

    CAS  PubMed  Google Scholar 

  19. Rodríguez AM, Monjo M, Roca P, Palou A (2002) Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cell Mol Life Sci 59:1714–1723

    PubMed  Google Scholar 

  20. Sarkar NN (2002) Mifepristone: bioavailability, pharmacokinetics and use-effectiveness. Eur J Obstet Gynecol Reprod Biol 101:113–120

    Article  CAS  PubMed  Google Scholar 

  21. Sitruk-Ware R, Spitz IM (2003) Pharmacological properties of mifepristone: toxicology and safety in animal and human studies. Contraception 68:409–420

    Article  CAS  PubMed  Google Scholar 

  22. Soumano K, Desbiens S, Rabelo R, Bakopanos E, Camirand A, Silva JE (2000) Glucocorticoids inhibit the transcriptional response of the uncoupling protein-1 gene to adrenergic stimulation in a brown adipose cell line. Mol Cell Endocrinol 165:7–15

    Article  CAS  PubMed  Google Scholar 

  23. Spitz IM (2002) Proven and potential clinical applications of mifpristone (RU486). Rev Endocr Metab Disord 3:267–275

    Article  CAS  PubMed  Google Scholar 

  24. Stock MJ (1989) Thermogenesis and brown fat: relevance to human obesity. Infusionstherapie 16:282–284

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Spanish Government: BFI2003-04439, FIS 01/1379 and Red temática de investigación cooperativa G03/028 and by the European Commission through The European NutriGenomics Organisation (NuGo), The Network of Excellence on Nutrition and Genomics (Contract No. FP6-506360).

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Correspondence to Andreu Palou.

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Rodríguez, A.M., Palou, A. The steroid RU486 induces UCP1 expression in brown adipocytes. Pflugers Arch - Eur J Physiol 449, 170–174 (2004). https://doi.org/10.1007/s00424-004-1329-7

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