Estrogen regulates neprilysin activity in rat brain

Jian Huang, Hanjun Guan, Rosemarie M. Booze, Christopher B. Eckman, Louis B. Hersh

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Neprilysin is a zinc metalloendopeptidase that regulates the activity of a number of physiological peptides through hydrolytic inactivation. Most recently, evidence has accumulated that neprilysin is involved in the clearance of amyloid β peptides in the brain. Previous studies have shown that the neprilysin gene responds to progesterone, androgen, and glucocorticoids. We now show that estrogen regulates neprilysin activity in rat brain. Ovariectomy leads to a 30% decrease in neprilysin activity at 45 or 85 days, but not 21 days, post surgery. Estrogen replacement restores neprilysin levels back to control values. These changes in neprilysin activity suggest that in women estrogen is required to maintain basal levels of neprilysin.

Original languageEnglish
Pages (from-to)85-87
Number of pages3
JournalNeuroscience Letters
Issue number1
StatePublished - Aug 26 2004

Bibliographical note

Funding Information:
Serum levels of estradiol, testosterone and progesterone were determined by the Ligand Assay and Analysis Core Laboratory of the University of Virginia. This core is supported by the NICHD/NIH through cooperative agreement U54 HD28934 as part of the specialized Cooperative Centers Program in Reproductive Research.

Funding Information:
This work was supported in part by grants from the Alzheimer’s Assn (L.B.H. and C.B.E.), the National Institute on Drug Abuse (DA02243 to L.B.H.; DA14401, DA13137, DA13712 to R.B.), the National Institute on Aging (AG19323 to L.B.H.), and the National Institute on Neurological Diseases and Stroke (NS042192 to C.B.E.).


  • Enzyme activity
  • Estrogen
  • Neprilysin
  • Ovariectomy

ASJC Scopus subject areas

  • Neuroscience (all)


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