Editors' ChoicePharmacology

Estrogen prodrug protects the brain

Sci. Signal.  28 Jul 2015:
Vol. 8, Issue 387, pp. ec206
DOI: 10.1126/scisignal.aad0860

Although estrogen is considered to heal the brain of many neurological and psychiatric symptoms, targeting the hormone to the brain only—and avoiding activity in other tissues—is no trivial feat. Prokai et al. discovered a “prodrug,” called DHED (10β,17β-dihydroxyestra-1,4-dien-3-one), that is selectively converted to one main estrogen, 17β-estradiol, only in the brain. Similar to 17β-estradiol itself, DHED protected menopausal female rodents from neurological symptoms of estrogen deprivation and also provided neuroprotection to rats after stroke, but without the negative systemic (specifically uterotrophic and cancerous) effects of the free hormone. With an efficacious and safe profile in vivo, this prodrug has the opportunity to provide positive estrogenic effects on the brain and relieve symptoms in patients with a broad range of central nervous system diseases.

L. Prokai, V. Nguyen, S. Szarka, P. Garg, G. Sabnis, H. A. Bimonte-Nelson, K. J. McLaughlin, J. S. Talboom, C. D. Conrad, P. J. Shughrue, T. D. Gould, A. Brodie, I. Merchenthaler, P. Koulen, K. Prokai-Tatrai, The prodrug DHED selectively delivers 17 β-estradiol to the brain for treating estrogen-responsive disorders. Sci. Transl. Med. 7, 297ra113 (2015). [Abstract]

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