GLUCOCORTICOID-SUPPRESSIBLE HYPERALDOSTERONISM AND ADRENAL-TUMORS OCCURRING IN A SINGLE FRENCH PEDIGREE

Glucocorticoid-suppressible hyperaldosteronism is a dominantly inherit ed form of hypertension believed to be caused by the presence of a hyb rid CYP11B1/CYP11B2 gene which has arisen from an unequal crossing ove r between the two CYP11B genes in a previous meiosis, We have studied a French pedigree with seven affected individuals in which two affecte d individuals also have adrenal tumors and two others have micronodula r adrenal hyperplasia, One of the adrenal tumors and the surrounding a drenal tissue has been removed, giving a rare opportunity to study the regulation and action of the hybrid gene causing the disease, The hyb rid CYP11B gene was demonstrated to be expressed at higher levels than either CYP11B1 or CYP11B2 in the cortex of the adrenal by RT-PCR and Northern blot analysis, In situ hybridization showed that both CYP11B1 and the hybrid gene were expressed in all three zones of the cortex. In cell culture experiments hybrid gene expression was stimulated by A CTH leading to increased production of aldosterone and the hybrid ster oids characteristic of glucocorticold-suppressible hyperaldosteronism. The genetic basis of the adrenal pathologies in this family is not kn own but may be related to the duplication causing the hyperaldosteroni sm.