IMMUNOFLUORESCENCE OF MINERALOCORTICOID RECEPTORS IN PERIPHERAL LYMPHOCYTES - PRESENCE OF RECEPTOR-LIKE ACTIVITY IN PATIENTS WITH THE AUTOSOMAL-DOMINANT FORM OF PSEUDOHYPOALDOSTERONISM, AND ITS ABSENCE IN THE RECESSIVE FORM

Pseudohypoaldosteronism is a syndrome characterized by salt wasting an d a failure to thrive due to the resistance towards the action of aldo sterone. Aldosterone levels and plasma renin activity are extremely el evated and aldosterone binding sites in peripheral mononuclear leukocy tes have regularly shown to be reduced or absent. Sporadic as well as familial cases have been identified and an autosomal dominant as well as an autosomal recessive mode of inheritance has been described. A de fect in the aldosterone receptor has been postulated, however, molecul ar genetic analysis in selected patients has not revealed a mutation i n the sequence of the coding region of the cDNA of the mineralocortico id receptor gene. In the present study we have used a fluorescence-lab eled antibody to detect possible receptor expression in monocytes from patients with various clinical forms of pseudohypoaldosteronism. Pati ents with the sporadic as well as with the autosomal dominant form wer e clearly immunopositive despite being negative in terms of aldosteron e receptor binding. In contrast in two patients with the autosomal rec essive form there was no detectable receptor protein, consistent with the results obtained in the aldosterone binding studies. These results suggest that the pathogenesis of pseudohypoaldosteronism is heterogen eous not only regarding the mode of inheritance but also in terms of r eceptor binding. Thus, in a subgroup of patients the inability of the receptor to bind ligand may be due to a defect involving other, probab ly cellular factors rather than a deficiency or a defect in the minera locorticoid receptor system itself.