AFLUID March 47/3

Husted, Russell F., Rita D. Sigmund, and John B. Stokes. Mechanisms of inactivation of the action of aldosterone on collecting duct by TGF-b. Am. J. Physiol. Renal Physiol. 278: F425–F433, 2000.—The purpose of these experiments was to investigate the mechanisms whereby transforming growth factor-b (TGF-b) antagonizes the action of adrenocorticoid hormones on Na1 transport by the rat inner medullary collecting duct in primary culture. Steroid hormones 1) increased Na1 transport by threeto fourfold, 2) increased the maximum capacity of the Na1-K1 pump by 30–50%, 3) increased the steady-state levels of the a1-subunit of the Na1-K1-ATPase by ,30%, and 4) increased the steadystate levels of the a-subunit of the rat epithelial Na1 channel (a-rENaC) by nearly fourfold. TGF-b blocked the effects of steroids on the increase in Na1 transport and the stimulation of the Na1-K1-ATPase and pump capacity. However, there was no effect of TGF-b on the steroid-induced increase in mRNA levels of a-rENaC. The effects of TGF-b were not secondary to the decrease in Na1 transport per se, inasmuch as benzamil inhibited the increase in Na1 transport but did not block the increase in pump capacity or Na1-K1-ATPase mRNA. The results indicate that TGF-b does not inactivate the steroid 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 increase in the transcription of a-rENaC.