Endocrinology, Vol 119, 2360-2367, Copyright © 1986 by Endocrine Society

ARTICLES

Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines

MA Pou, J Bismuth, J Gharbi-Chihi and J Torresani

As previously reported, preadipocytes cloned from the epididymal fat of lean or genetically obese mice (HGFu and ob 17, respectively) contain the nuclear T3 receptor. The number of receptor sites was similar in confluent cells of both lines and approximately doubled during adipocyte differentiation. T3 added to the culture medium increased triacylglycerol synthesis. T3 also increased fatty acid synthase specific activity, relative synthesis rate, and relative mRNA content (1.5- to 2.5-fold). Optimal responses were obtained at 1.5 nM. This study shows that under the same culture conditions in both cell lines, 1.5 nM T3 decreased the receptor concentration with no significant change in the affinity for T3. The receptor depletion was time dependent, rapid, stable in the presence of T3, and reversible in less than 24 h after its withdrawal. Receptor depletion was also dependent on T3 concentration and close to maximum at 1.5 nM T3 [45.1 +/- 2.7% (+/- SE) of the data values without T3; n = 14]. A linear relationship was observed between receptor occupancy by T3 and receptor loss. T4 and triiodothyroacetic acid also decreased the T3 receptor content, as expected from their own affinity for the receptor. These last two observations suggest that the receptor reduction is related to its occupancy by T3. The reported results, also observed in several other cell types, indicate that down-regulation of the nuclear T3 receptor by thyroid hormones is probably a generalized event in T3 target cells at least in vitro. Interpretation of its significance in preadipocyte cell lines requires further studies of rapid nuclear events following T3 receptor occupancy.