Evidence that Brown Adipose Tissue Is a Glucocorticoid Target Organ*

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Abstract
The interscapular fat pad from adrenalectomized rats was used in steroid-binding experiments to ascertain whether brown adipose tissue [BAT] contained glucocorticoid receptors. Bound and free steroids were separated by Sephadex chromatography. The time course of [3H]dexamethasone (9.alpha.-fluoro-16.alpha.-methyl-16.beta.,17.alpha.,21-trihydroxypregna-1,4-diene-3,20-dione) binding to BAT cytosol reached a plateau between 1 and 2 h at 0.degree. C and remained stable for 5 h; there was extensive decay by 24 h. Cytosol incubated with increasing concentrations of [3H]dexamethasone for 3 h at 0.degree. C exhibited a saturable number of binding sites. Scatchard analysis showed the binding to be to a homogeneous class of binding sites with an apparent dissociation constant of 6.5 nM and a concentration of 161 fmol/mg cytosol protein. The relative potency of a variety of steroids for the BAT-binding site was assessed by competitive binding assay. The site resembled other glucocorticoid receptors, exhibiting high affinity for dexamethasone and corticosterone, intermediate affinity for progesterone and cortexolone, and low affinity for testosterone and estradiol. Temperature-dependent translocation of the [3H]dexamethasone-receptor complex to the nucleus could be demonstrated. It was also shown that the receptor was present in isolated adipocytes, excluding the possibility that the binding site was actually limited to stromal elements and not present in BAT cells. A function of glucorcorticoids in the isolated adipocytes was detected. Dexamethasone caused the inhibition of uridine incorporation into trichloroacetic acid-precipitable material. The effect was dose dependent, glucocorticoid specific and required a latent period; all of these features are compatible with a receptor-mediated function. BAT is a glucocorticoid target organ.