Mechanisms of inactivation of the action of aldosterone on collecting ductby TGF-beta

The purpose of these experiments was to investigate the mechanisms whereby transforming growth factor-beta (TGF-beta) antagonizes the action of adreno corticoid hormones on Na+ transport by the rat inner medullary collecting d uct in primary culture. Steroid hormones 1) increased Na+ transport by thre e- to fourfold, 2) increased the maximum capacity of the Na+-K+ pump by 30- 50%, 3) increased the steady-state levels of the alpha(1)-subunit of the Na +-K+-ATPase by similar to 30%, and 4) increased the steady-state levels of the alpha-subunit of the rat epithelial Na+ channel (alpha-rENaC) by nearly fourfold. TGF-beta blocked the effects of steroids on the increase in Natransport and the stimulation of the Na+-K+-ATPase and pump capacity. Howev er, there was no effect of TGF-beta on the steroid-induced increase in mRNA levels of alpha-rENaC. The effects of TGF-beta were not secondary to the d ecrease in Na+ transport per se, inasmuch as benzamil inhibited the increas e in Na+ transport but did not block the increase in pump capacity or Na+-K +-ATPase mRNA. The results indicate that TGF-beta does not inactivate the s teroid receptor or its translocation to the nucleus. Rather, they indicate complex pathways involving interruption of the enhancement of pump activity and activation/inactivation of pathways distal to the steroid-induced incr ease in the transcription of alpha-rENaC.