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G-protein coupled estrogen receptor, estrogen receptor ?, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment.

ABSTRACT: Steroid hormone receptors are widely and heterogeneously expressed in the brain, and are regulated by age and gonadal hormones. Our goal was to quantify effects of aging, long-term estradiol (E2 ) treatment, and their interactions, on expression of G protein-coupled estrogen receptor (GPER), estrogen receptor ? (ER?) and progesterone receptor (PR) immunoreactivity in two hypothalamic regions, the arcuate (ARC) and the periventricular area (PERI) of rhesus monkeys as a model of menopause and hormone replacement. Ovariectomized (OVX) rhesus macaques were young (? 11 years) or aged (? 25 years), given oil (vehicle) or E2 every 3 weeks for 2 years. Immunohistochemistry and stereologic analysis of ER?, PR, and GPER was performed. More effects were detected for GPER than the other two receptors. Specifically, GPER cell density in the ARC and PERI, and the percent of GPER-immunoreactive cells in the PERI, were greater in aged than in young monkeys. In addition, we mapped the qualitative distribution of GPER in the monkey hypothalamus and nearby regions. For ER?, E2 treated monkeys tended to have higher cell density than vehicle monkeys in the ARC. The percent of PR density in the PERI tended to be higher in E2 than vehicle monkeys of both ages. This study shows that the aged hypothalamus maintains expression of hormone receptors with age, and that long-term cyclic E2 treatment has few effects on their expression, although GPER was affected more than ER? or PR. This result is surprising in light of evidence for E2 regulation of the receptors studied here, and differences may be due to the selected regions, long-term nature of E2 treatment, among other possibilities.

SUBMITTER: Naugle MM

PROVIDER: S-EPMC4282650 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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G-protein coupled estrogen receptor, estrogen receptor α, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment.

Naugle Michelle M MM Nguyen Long T LT Merceron Tyler K TK Filardo Edward E Janssen William G M WG Morrison John H JH Rapp Peter R PR Gore Andrea C AC

Journal of experimental zoology. Part A, Ecological genetics and physiology 20140524 7

Steroid hormone receptors are widely and heterogeneously expressed in the brain, and are regulated by age and gonadal hormones. Our goal was to quantify effects of aging, long-term estradiol (E2 ) treatment, and their interactions, on expression of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα) and progesterone receptor (PR) immunoreactivity in two hypothalamic regions, the arcuate (ARC) and the periventricular area (PERI) of rhesus monkeys as a model of menopause and horm ...[more]

PMID: 24862737

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Project description:BACKGROUND:The origin of nuclear receptors (NRs) and the question whether the ancestral NR was a liganded or an unliganded transcription factor has been recently debated. To obtain insight into the evolution of the ligand binding ability of estrogen receptors (ER), we comparatively characterized the ER from the protochordate amphioxus (Branchiostoma floridae), and the ER from lamprey (Petromyzon marinus), a basal vertebrate. RESULTS:Extensive phylogenetic studies as well as signature analysis allowed us to confirm that the amphioxus ER (amphiER) and the lamprey ER (lampER) belong to the ER group. LampER behaves as a "classical" vertebrate ER, as it binds to specific DNA Estrogen Responsive Elements (EREs), and is activated by estradiol (E2), the classical ER natural ligand. In contrast, we found that although amphiER binds EREs, it is unable to bind E2 and to activate transcription in response to E2. Among the 7 natural and synthetic ER ligands tested as well as a large repertoire of 14 cholesterol derivatives, only Bisphenol A (an endocrine disruptor with estrogenic activity) bound to amphiER, suggesting that a ligand binding pocket exists within the receptor. Parsimony analysis considering all available ER sequences suggest that the ancestral ER was not able to bind E2 and that this ability evolved specifically in the vertebrate lineage. This result does not support a previous analysis based on ancestral sequence reconstruction that proposed the ancestral steroid receptor to bind estradiol. We show that biased taxonomic sampling can alter the calculation of ancestral sequence and that the previous result might stem from a high proportion of vertebrate ERs in the dataset used to compute the ancestral sequence. CONCLUSION:Taken together, our results highlight the importance of comparative experimental approaches vs ancestral reconstructions for the evolutionary study of endocrine systems: comparative analysis of extant ERs suggests that the ancestral ER did not bind estradiol and that it gained the ability to be regulated by estradiol specifically in the vertebrate lineage, before lamprey split.

Dataset Information

G-protein coupled estrogen receptor, estrogen receptor ?, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment.

Publications

G-protein coupled estrogen receptor, estrogen receptor α, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment.

Similar Datasets

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