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Transcriptional control of sodium transport in tight epithelia by adrenal steroids

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Conclusions

The model for the adrenal steroid action on Na transport in tight epithelia as depicted in Fig. 3A and B dissociates two phases: an early phase during which the pre-existing Na transport machinery is activated and a late phase during which the transport capacity of the machinery is increased. These two sequential phases have been distinguished based on differences in functional aspects of the induced transport, on selective effects of agents interfering with transcriptional regulation and on a correlation of the late response phase with an increase in transport protein synthesis and expression [26, 45, 46, 98, 99, 124]. These observations suggest that a bimodal stimulation of Na transport could involve two different gene networks which are directly (in the physiological meaning) and independently stimulated by the action of the hormone-receptor complex and the following “molecular” cascades (see section Molecular and Physiological Cascades). The relatively clear temporal dissociation of the responses found in experimental situations is probably the consequence of inherent properties of the two networks. Indeed, to generate rapid functional changes, the genes involved in the early response must encode products which have relatively short half-lifes at the mRNA and protein levels. In contrast, the constitutive elements of the Na transport machinery that are increased during the late phase of adrenal steroid action have, as shown for the Na,K-ATPase [82], relatively long half-lifes. Consequently, even though changes in transcription may take place early in the course of the hormonal treatment, they impact on protein synthesis and pools only slowly and after a substantial lag period.

On the one hand, ongoing research will soon provide more information on the nature, time course and hormone/receptor specificity of adrenal-steroid-regulated genes. On the other hand, the availability of new technical and molecular tools to study the proteins of the Na transport machinery greatly increases the possibilities for studying its regulation by adrenal steroids. Consequently, it will be a fascinating challenge to relate the data emerging from both approaches, and it appears that only a combination of methods and tools will allow to progressively fill the gap of understanding which still lies between the transcriptional effects and the transport regulation.

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  1. Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland

    F. Verrey

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I wish to thank Bernard Rossier, Jörg Beron and Gillian Hayes for reading the manuscript, Bernard Rossier, Alex Puoti, Haim Garty and Anikó Náray-Fejes-Tóth for the communication of unpublished results, and Christian Gasser for the artwork. The laboratory of the author is supported by Grant 31-39499-93 from the Swiss National Science Foundation and by the Olga Mayenfisch Stiftung, Zürich.

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Verrey, F. Transcriptional control of sodium transport in tight epithelia by adrenal steroids. J. Membarin Biol. 144, 93–110 (1995). https://doi.org/10.1007/BF00232796

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