These results suggest that, in chondrocytes, NO is a key regulator of the signaling pathways leading from IL-I to NF-kappaB and AP-1 activation and to the expression of genes that are involved in the pathophysiology of arthritic diseases.

The aim of this work was to compare the subcellular distribution of the oestrogen receptor from the uteri of rats treated with vehicle alone (control group), oestradiol or one of the anti-oestrogenic drugs tamoxifen and ZD 182,780. The nuclear, microsomal and cytosolic oestrogen receptor contents were evaluated by an immunoenzymatic method ("ER-EIA" kit from Abbott Laboratories) and the results in each fraction were expressed as a percentage of the total number of receptors. Parallel studies were performed to assess the uterotrophic effect of these drugs and to assess that they had reached the uterus. In the control group, we found that the oestrogen receptor was distributed mainly between the microsomal (29.1 +/- 1.3%) and cytosolic (68.1 +/- 0.9%) fractions, with only a small amount located in the nucleus (2.8 +/- 0.5%). When oestradiol was administered, the oestrogen receptor distribution was: nuclear 11.7 +/- 2.0, microsomal 15.5 +/- 1.3 and cytosolic 72.8 +/- 3.3% and, in the tamoxifen group, the results were: nuclear 18.5 +/- 1.5, microsomal 26.0 +/- 3.1 and cytosolic 55.5 +/- 3.4%, which shows a relative shift both to the control and the oestradiol-treated groups. In the uteri of rats treated with ZD 182,780 the results were very similar to those obtained in the control group. Our results indicate that the subcellular distribution of the oestrogen receptor varies according to the drug administered and that this receptor may not be located in a single subcellular compartment. Moreover, the nuclear uptake of the ZD 182,780-oestrogen receptor complex seems to be blocked, possibly due to impaired receptor dimerization. In the case of tamoxifen, the intracellular transport of the receptor also seems to be blocked, probably due to the nuclear retention of the receptor, thus suggesting that tamoxifen must impair the oestrogen receptor function on a step subsequent to the receptor dimerization.