Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles.
This study investigated the impact of chronic exposure to continuous (CoP4) versus cyclic progesterone (CyP4) alone or in combination with 17β-estradiol (E2) on gene expression profiles targeting bioenergetics, metabolism and inflammation in the adult female rat hippocampus. High-throughput qRT-PCR...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3290616?pdf=render |
id |
doaj-29a90961d2dc4f9dbafced21b57c30d7 |
---|---|
record_format |
Article |
spelling |
doaj-29a90961d2dc4f9dbafced21b57c30d72020-11-25T02:08:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3126710.1371/journal.pone.0031267Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles.Liqin ZhaoTodd E MorganZisu MaoSharon LinEnrique CadenasCaleb E FinchChristian J PikeWendy J MackRoberta D BrintonThis study investigated the impact of chronic exposure to continuous (CoP4) versus cyclic progesterone (CyP4) alone or in combination with 17β-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 α subunit; Atp5a1), redox homeostasis (peroxiredoxin 5; Prdx5), insulin signaling (insulin-like growth factor I; Igf1), and cholesterol trafficking (liver X receptor α subtype; Nr1h3), differed in direction of regulation by E2+CoP4 (down-regulation relative to OVX) and E2+CyP4 (up-regulation relative to OVX). In contrast, genes involved in amyloid metabolism (β-secretase; Bace1) differed only in degree of regulation, as both E2+CoP4 and E2+CyP4 induced down-regulation at different efficacy. E2+CyP4-induced changes could be associated with regulation of progesterone receptor membrane component 1(Pgrmc1). In summary, results from this study provide evidence at the molecular level that differing regimens of hormone therapy (HT) can induce disparate gene expression profiles in brain. From a translational perspective, confirmation of these results in a model of natural menopause, would imply that the common regimen of continuous combined HT may have adverse consequences whereas a cyclic combined regimen, which is more physiological, could be an effective strategy to maintain neurological health and function throughout menopausal aging.http://europepmc.org/articles/PMC3290616?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liqin Zhao Todd E Morgan Zisu Mao Sharon Lin Enrique Cadenas Caleb E Finch Christian J Pike Wendy J Mack Roberta D Brinton |
spellingShingle |
Liqin Zhao Todd E Morgan Zisu Mao Sharon Lin Enrique Cadenas Caleb E Finch Christian J Pike Wendy J Mack Roberta D Brinton Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. PLoS ONE |
author_facet |
Liqin Zhao Todd E Morgan Zisu Mao Sharon Lin Enrique Cadenas Caleb E Finch Christian J Pike Wendy J Mack Roberta D Brinton |
author_sort |
Liqin Zhao |
title |
Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
title_short |
Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
title_full |
Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
title_fullStr |
Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
title_full_unstemmed |
Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
title_sort |
continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
This study investigated the impact of chronic exposure to continuous (CoP4) versus cyclic progesterone (CyP4) alone or in combination with 17β-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 α subunit; Atp5a1), redox homeostasis (peroxiredoxin 5; Prdx5), insulin signaling (insulin-like growth factor I; Igf1), and cholesterol trafficking (liver X receptor α subtype; Nr1h3), differed in direction of regulation by E2+CoP4 (down-regulation relative to OVX) and E2+CyP4 (up-regulation relative to OVX). In contrast, genes involved in amyloid metabolism (β-secretase; Bace1) differed only in degree of regulation, as both E2+CoP4 and E2+CyP4 induced down-regulation at different efficacy. E2+CyP4-induced changes could be associated with regulation of progesterone receptor membrane component 1(Pgrmc1). In summary, results from this study provide evidence at the molecular level that differing regimens of hormone therapy (HT) can induce disparate gene expression profiles in brain. From a translational perspective, confirmation of these results in a model of natural menopause, would imply that the common regimen of continuous combined HT may have adverse consequences whereas a cyclic combined regimen, which is more physiological, could be an effective strategy to maintain neurological health and function throughout menopausal aging. |
url |
http://europepmc.org/articles/PMC3290616?pdf=render |
work_keys_str_mv |
AT liqinzhao continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT toddemorgan continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT zisumao continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT sharonlin continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT enriquecadenas continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT calebefinch continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT christianjpike continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT wendyjmack continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles AT robertadbrinton continuousversuscyclicprogesteroneexposuredifferentiallyregulateshippocampalgeneexpressionandfunctionalprofiles |
_version_ |
1724927506009554944 |