17β-Estradiol and progesterone regulate expression of β-amyloid clearance factors in primary neuron cultures and female rat brain

Anusha Jayaraman, Jenna C. Carroll, Todd E. Morgan, Sharon Lin, Liqin Zhao, Jason M. Arimoto, M. Paul Murphy, Tina L. Beckett, Caleb E. Finch, Roberta Diaz Brinton, Christian J. Pike

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The accumulation of β-amyloid protein (Aβ) is a key risk factor in the development of Alzheimer's disease. The ovarian sex steroid hormones 17β-estradiol (E2) and progesterone (P4) have been shown to regulate Aβ accumulation, although the underlying mechanism(s) remain to be fully elucidated. In this study, we investigate the effects of E2 and P4 treatment on the expression levels of Aβ clearance factors including insulin-degrading enzyme, neprilysin, endothelin-converting enzyme 1 and 2, angiotensin-converting enzyme, and transthyretin, both in primary neuron cultures and female rat brains. Our results show that E2 and P4 affect the expression levels of several Aβ clearance factors in dose- and time-dependent manners. Most notably, expression of insulin-degrading enzyme is significantly increased by both hormones in cultured neurons and in vivo and is inversely associated with the soluble Aβ levels in vivo. These findings further define sex steroid hormone actions involved in regulation of Aβ, a relationship potentially important to therapeutic approaches aimed at reducing risk of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)5467-5479
Number of pages13
JournalEndocrinology
Volume153
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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