Stimulation of membrane-bound guanylate cyclase activity by 17-beta estradiol

Biochem Biophys Res Commun. 1998 Nov 27;252(3):639-42. doi: 10.1006/bbrc.1998.9716.


Estrogen is known to exert both long-term genomic and short-term nongenomic actions. The long-term genomic actions of estrogen are mediated by the binding of estrogen to its cytoplasmic/nuclear receptor that subsequently triggers the transcription of target genes. In contrast, little is known about the molecular basis of the nongenomic actions of estrogen. We have found that 17-beta estradiol activates membrane-bound guanylate cyclase and enhances atrial natriuretic factor (ANF)-stimulated guanylate cyclase activity in PC12 cell membranes. Membrane-bound guanylate cyclase, GC-A, contains an extracellular ANF-binding domain and an intracellular kinase-like domain plus catalytic domain. The kinase-like domain plus the catalytic domain of guanylate cyclase (GC-kc) can be expressed in E. Coli and functionally renatured. 17-beta estradiol also activates the bacteria expressed GC-kc, indicating that 17-beta estradiol can directly interact with membrane-bound guanylate cyclase. These results demonstrate that 17-beta estradiol exerts a non-genomic action on membrane-bound guanylate cyclase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Cell Membrane / enzymology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Estradiol / pharmacology*
  • Guanylate Cyclase / metabolism*
  • PC12 Cells
  • Rats


  • Estradiol
  • Guanylate Cyclase