3alpha,5alpha-THP mediates progestins' effects to protect against adrenalectomy-induced cell death in the dentate gyrus of female and male rats

Pharmacology, Biochemistry, and Behavior
M E RhodesC A Frye

Abstract

Progestins have neuroprotective effects in several in vitro models of neurodegeneration and in vivo in seizure models. The extent to which progesterone's in vivo protective effects may generalize to models not involving seizure processes and whether progesterone's protective effects are modulated by its metabolites have not been comprehensively investigated. The present experiments investigated the effects of progesterone and its metabolites, dihydryoprogesterone (DHP) and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), to protect the hippocampus from damage induced by adrenalectomy (ADX). In Experiments 1 and 2, progesterone, DHP, or 3alpha,5alpha-THP administration (1 mg/kg sc) to female (Experiment 1) or male (Experiment 2) rats similarly reduced the total number of ADX-induced pyknotic cells in the dentate gyrus compared with vehicle administration. In Experiment 3, blocking progesterone's metabolism to 3alpha,5alpha-THP with coadministration of a 5alpha-reductase inhibitor, finasteride (10 mg/kg sc), in female rats attenuated progesterone's protective effects on cell death in the dentate gyrus. Together, these data suggest that progestins can protect against ADX-induced cell death and that the actions of the progester...Continue Reading

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Citations

Oct 1, 2009·Future Medicinal Chemistry·Cheryl A Frye
Apr 9, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Jason J Paris, Cheryl A Frye
Nov 9, 2007·Neurobiology of Learning and Memory·Cheryl A Frye, Alicia A Walf
Mar 15, 2006·Neurobiology of Learning and Memory·Alicia A WalfCheryl A Frye
Jul 13, 2006·Expert Review of Neurotherapeutics·Cheryl A Frye
Jul 30, 2010·Stress : the International Journal on the Biology of Stress·Paula J Brunton, John A Russell
May 1, 2020·Frontiers in Behavioral Neuroscience·Cheryl A Frye, Sridar V Chittur
Nov 3, 2010·Stress : the International Journal on the Biology of Stress·Jason J Paris, Cheryl A Frye

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