NEUROENDOCRINOLOGYMnemonic effects of progesterone to mice require formation of 3α,5α-THPFrye, Cheryl A.; Koonce, Carolyn J.; Walf, Alicia A.Author Information Departments of Psychology, Biology, Centers for Life Science and Neuroscience Research, University at Albany-SUNY, Albany, New York, USA Correspondence to Cheryl Frye, PhD, Departments of Psychology, Biology, and Centers for Life Science and Neuroscience Research, University at Albany-SUNY, Life Sciences Research Building, 1400 Washington Avenue, Albany, NY 12222, USA Tel: +1 518 591 8839; fax: +1 518 591 8848; e-mail: firstname.lastname@example.org Received 11 March 2010 accepted 31 March 2010 NeuroReport: June 2nd, 2010 - Volume 21 - Issue 8 - p 590-595 doi: 10.1097/WNR.0b013e32833a7e14 Buy SDC Metrics Abstract Ovarian hormones organize and activate neural circuits for reproduction and may also mediate cognition. Research has focused on estradiol's mnemonic effects, albeit progesterone covaries with estradiol and its mechanisms for cognition require attention. Studies tested the hypothesis that cognitive effects of progesterone occur subsequent to its metabolism to 5α-pregnan-3α-ol-20-one (3α,5α-THP), which does not bind progestin receptors. Cognitive performance and progestogen levels in plasma, hippocampus, and cortex were determined in ovariectomized mice administered vehicle, or progestins that differentially form 3α,5α-THP and bind progestin receptors (progesterone, 3α,5α-THP, and/or medroxyprogesterone acetate). Only treatments that increased 3α,5α-THP levels during memory consolidation (progesterone, 3α,5α-THP, 3α-5α-THP plus medroxyprogesterone acetate, but not progesterone plus medroxyprogesterone acetate) improved cognitive performance. Thus, formation of 3α,5α-THP may be required for progesterone's cognitive-enhancing effects. © 2010 Lippincott Williams & Wilkins, Inc.