La régulation pluri-hormonale intégrée des fonctions rénales

Abstract

The kidney is the main organ regulating the composition of the body fluids. A considerable number of hormones controls the activity of the renal cells to maintain the equilibrium of the hydromineral balance. It becomes more and more difficult to interpret this multi-hormonal control in terms of regulatory processes. For illustrating this complexity, the hormonal regulation of the electrolyte transport in the nephron thick ascending limb is taken as an example. This nephron segment is very directly responsible for two kidney functions: the urinary concentrating ability (by its capacity to transport hypertonic sodium chloride) and the regulation of magnesium excretion into final urine' Six hormones are presently identified as acting on the transport of both NaCl and Mg2+ in this nephron segment. The question is therefore to determine how the thick ascending limb and, hence, the kidney, is capable of regulating the water balance independently form the magnesium balance. It is proposed that the hormones act in a combinatorial mode: the circulating levels of each of the hormones acting on these cells would settle the configuration of the paracellular and transcellular transport pathways of the epithelium either in the << sodium >> or << magnesium >> mode. The configuration would depend on the distribution of the receptor isoforms at the surface of the basolateral membrane: this distribution may vary according to factors such as age. nutritional variability, hormonal status, degree of desensitization of the receptors, etc. The modulation of the hormonal responses would depend on the degree of coupling of the hormone-receptor complexes to the different intracellular transduction pathways and on the resulting negative and/or positive interactions between these pathways.