Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2

Leigh Pascoe, Kathleen M. Curnow, Liliya Slutsker, John M C Connell, Phyllis W. Speiser, Maria I. New, Perrin C. White

Research output: Contribution to journalArticlepeer-review

240 Scopus citations


Glucocorticoid-suppressible hyperaldosteronism (GSH) is an autosomal dominant form of familial hypertension. The biochemical abnormalities seen in this disorder may be remedied by administration of dexamethasone, implying that aldosterone synthesis is being abnormally regulated by corticotropin. The final three steps of aldosterone synthesis, 11β- and 18-hydroxylation and 18-oxidation, are mediated by a cytochrome P450 in the zona glomerulosa of the adrenal cortex termed CYP11B2. A related isozyme in the zona fasciculate, CYP11B1, is required for cortisol synthesis; this isozyme, which is normally expressed at much higher levels than CYP11B2, only has 11β-hydroxylase activity. These isozymes are encoded by genes on human chromosome 8q22. We have now studied four unrelated patients with GSH. We found that each patient has one chromosome that carries three CYP11B genes instead of two. This has presumably been generated by unequal meiotic crossing-over. The extra gene is a hybrid with 5′ regulatory and coding regions corresponding to CYP11B1 and 3′ coding regions from CYP11B2. The break-point is in intron 2 in two cases, intron 3 in one, and exon 4 in one. Cells transfected with hybrid cDNAs containing up to the first three exons of CYP11B1 synthesized aldosterone at levels near that of cells carrying normal CYP11B2, but cells transfected with hybrids containing the first five or more exons of CYP11B1 could not synthesize detectable amounts of aldosterone. These data demonstrate that GSH is caused by expression of a gene that is regulated like CYP11B1 but that encodes a protein able to synthesize aldosterone. (.

Original languageEnglish (US)
Pages (from-to)8327-8331
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - 1992


  • Aldosterone synthase
  • Dexamethasone-suppressible hyperaldosteronism
  • Glucocorticoid remediable aldosteronism
  • Hypertension
  • Steroid 11-hydroxylase

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2'. Together they form a unique fingerprint.

Cite this