Thermogenic effects of the antiglucocorticoid RU-486 in the rat: Involvement of corticotropin-releasing factor and sympathetic activation of brown adipose tissue

A. J. Hardwick, E. A. Linton, N. J. Rothwell

Research output: Contribution to journalArticlepeer-review

Abstract

Acute injection (sc) of the antiglucocorticoid RU-486 (5-10 mg/kg) stimulated oxygen consumption (VO2) and brown adipose tissue (BAT) activity (mitochondrial GDP binding) in the rat. A peak effect was seen 60-80 min after injection. The rise in VO2 was prevented by prior injection of the β-adrenergic antagonist propranolol, and the effect on BAT was abolished by surgical denervation of the sympathetic supply to the tissue. Central injection (cerebroventricular) of a much lower dose (3-8 μg/kg) of RU-486 also stimulated VO2, and this effect was inhibited by a CRF receptor antagonist [α-helical CRF-(9-41)]. Peripheral injection of RU-486 also elicited acute thermogenic responses in older (> 12 months) rats and in genetically obese (Zucker) rats. In lean animals, daily injection of RU-486 inhibited weight gain and stimulated BAT without affecting food intake. The thermogenic effects of RU-486 apear to be due to central stimulation of sympathetic outflow and may involve CRF release. The data support previous studies on the effects of adrenalectomy and CRF on thermogenesis in the rat.
Original languageEnglish
Pages (from-to)1684-1688
Number of pages4
JournalEndocrinology
Volume124
Issue number4
Publication statusPublished - 1989

Keywords

  • metabolism: Adipose Tissue
  • Animals
  • Body Temperature
  • physiology: Corticotropin-Releasing Hormone
  • pharmacology: Estrenes
  • antagonists & inhibitors: Glucocorticoids
  • Male
  • Mifepristone
  • drug effects: Oxygen Consumption
  • Rats
  • Rats, Inbred Strains
  • Support, Non-U.S. Gov't
  • physiology: Sympathetic Nervous System

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