continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles连续与循环孕激素暴露不同调节海马基因表达和功能配置文件.pdfVIP

Continuous versus Cyclic Progesterone Exposure Differentially Regulates Hippocampal Gene Expression and Functional Profiles 1 2 1 2 1 2 Liqin Zhao *, Todd E. Morgan , Zisu Mao , Sharon Lin , Enrique Cadenas , Caleb E. Finch , Christian J. 2 3 1,4 Pike , Wendy J. Mack , Roberta D. Brinton * 1 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, United States of America, 2 Davis School of Gerontology, University of Southern California, Los Angeles, California, United States of America, 3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, 4 Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America Abstract This study investigated the impact of chronic exposure to continuous (CoP4) versus cyclic progesterone (CyP4) alone or in combination with 17b-estradiol (E2) on gene expression profiles targeting bioenergetics, metabolism and inflammation in the adult female rat hippocampus. High-throughput qRT-PCR analyses revealed that ovarian hormonal depletion induced by ovariectomy (OVX) led to multiple significant gene expression alterations, which were to a great extent reversed by co- administration of E2 and CyP4. In contrast, co-administration of E2 and CoP4 induced a pattern highly resembling OVX. Bioinformatics analyses further revealed clear disparities in functional profiles associated with E2+CoP4 and E2+CyP4. Genes involved in mitochondrial energy (ATP synthase a subunit; Atp5a1), redox homeostasis (peroxiredoxin 5; Prd