Cargando…
RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus
In females, estrogens have two main modes of action relating to gonadotropin secretion: positive feedback and negative feedback. Estrogen positive and negative feedback are controlled by different regions of the hypothalamus: the preoptic area/anterior portion (mainly the anteroventral periventricul...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372949/ https://www.ncbi.nlm.nih.gov/pubmed/34407144 http://dx.doi.org/10.1371/journal.pone.0256148 |
_version_ | 1783739861500428288 |
---|---|
author | Mohr, Margaret A. Wong, Angela M. Sukumar, Gauthaman Dalgard, Clifton L. Hong, Weizhe Wu, T. John Wu, Ye Emily Micevych, Paul E. |
author_facet | Mohr, Margaret A. Wong, Angela M. Sukumar, Gauthaman Dalgard, Clifton L. Hong, Weizhe Wu, T. John Wu, Ye Emily Micevych, Paul E. |
author_sort | Mohr, Margaret A. |
collection | PubMed |
description | In females, estrogens have two main modes of action relating to gonadotropin secretion: positive feedback and negative feedback. Estrogen positive and negative feedback are controlled by different regions of the hypothalamus: the preoptic area/anterior portion (mainly the anteroventral periventricular nucleus, AVPV) of the hypothalamus is associated with estrogen positive feedback while the mediobasal hypothalamus (mainly the arcuate nucleus of the hypothalamus, ARH), is associated with estrogen negative feedback. In this study, we examined the temporal pattern of gene transcription in these two regions following estrogen treatment. Adult, ovariectomized, Long Evans rats received doses of estradiol benzoate (EB) or oil every 4 days for 3 cycles. On the last EB priming cycle, hypothalamic tissues were dissected into the AVPV+ and ARH+ at 0 hrs (baseline/oil control), 6 hrs, or 24 hrs after EB treatment. RNA was extracted and sequenced using bulk RNA sequencing. Differential gene analysis, gene ontology, and weighted correlation network analysis (WGCNA) was performed. Overall, we found that the AVPV+ and ARH+ respond differently to estradiol stimulation. In both regions, estradiol treatment resulted in more gene up-regulation than down-regulation. S100g was very strongly up-regulated by estradiol in both regions at 6 and 24 hrs after EB treatment. In the AVPV+ the highest number of differentially expressed genes occurred 24 hrs after EB. In the ARH+, the highest number of genes differentially expressed by EB occurred between 6 and 24 hrs after EB, while in the AVPV+, the fewest genes changed their expression between these time points, demonstrating a temporal difference in the way that EB regulates transcription these two areas. Several genes strongly implicated in gonadotropin release were differentially affected by estradiol including Esr1, encoding estrogen receptor-α and Kiss1, encoding kisspeptin. As an internal validation, Kiss1 was up-regulated in the AVPV+ and down-regulated in the ARH+. Gene network analysis revealed the vastly different clustering of genes modulated by estradiol in the AVPV+ compared with the ARH+. These results indicate that gene expression in these two hypothalamic regions have specific responses to estradiol in timing and direction. |
format | Online Article Text |
id | pubmed-8372949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83729492021-08-19 RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus Mohr, Margaret A. Wong, Angela M. Sukumar, Gauthaman Dalgard, Clifton L. Hong, Weizhe Wu, T. John Wu, Ye Emily Micevych, Paul E. PLoS One Research Article In females, estrogens have two main modes of action relating to gonadotropin secretion: positive feedback and negative feedback. Estrogen positive and negative feedback are controlled by different regions of the hypothalamus: the preoptic area/anterior portion (mainly the anteroventral periventricular nucleus, AVPV) of the hypothalamus is associated with estrogen positive feedback while the mediobasal hypothalamus (mainly the arcuate nucleus of the hypothalamus, ARH), is associated with estrogen negative feedback. In this study, we examined the temporal pattern of gene transcription in these two regions following estrogen treatment. Adult, ovariectomized, Long Evans rats received doses of estradiol benzoate (EB) or oil every 4 days for 3 cycles. On the last EB priming cycle, hypothalamic tissues were dissected into the AVPV+ and ARH+ at 0 hrs (baseline/oil control), 6 hrs, or 24 hrs after EB treatment. RNA was extracted and sequenced using bulk RNA sequencing. Differential gene analysis, gene ontology, and weighted correlation network analysis (WGCNA) was performed. Overall, we found that the AVPV+ and ARH+ respond differently to estradiol stimulation. In both regions, estradiol treatment resulted in more gene up-regulation than down-regulation. S100g was very strongly up-regulated by estradiol in both regions at 6 and 24 hrs after EB treatment. In the AVPV+ the highest number of differentially expressed genes occurred 24 hrs after EB. In the ARH+, the highest number of genes differentially expressed by EB occurred between 6 and 24 hrs after EB, while in the AVPV+, the fewest genes changed their expression between these time points, demonstrating a temporal difference in the way that EB regulates transcription these two areas. Several genes strongly implicated in gonadotropin release were differentially affected by estradiol including Esr1, encoding estrogen receptor-α and Kiss1, encoding kisspeptin. As an internal validation, Kiss1 was up-regulated in the AVPV+ and down-regulated in the ARH+. Gene network analysis revealed the vastly different clustering of genes modulated by estradiol in the AVPV+ compared with the ARH+. These results indicate that gene expression in these two hypothalamic regions have specific responses to estradiol in timing and direction. Public Library of Science 2021-08-18 /pmc/articles/PMC8372949/ /pubmed/34407144 http://dx.doi.org/10.1371/journal.pone.0256148 Text en © 2021 Mohr et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mohr, Margaret A. Wong, Angela M. Sukumar, Gauthaman Dalgard, Clifton L. Hong, Weizhe Wu, T. John Wu, Ye Emily Micevych, Paul E. RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title | RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title_full | RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title_fullStr | RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title_full_unstemmed | RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title_short | RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
title_sort | rna-sequencing of avpv and arh reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372949/ https://www.ncbi.nlm.nih.gov/pubmed/34407144 http://dx.doi.org/10.1371/journal.pone.0256148 |
work_keys_str_mv | AT mohrmargareta rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT wongangelam rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT sukumargauthaman rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT dalgardcliftonl rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT hongweizhe rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT wutjohn rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT wuyeemily rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus AT micevychpaule rnasequencingofavpvandarhrevealsvastlydifferenttemporalandtranscriptomicresponsestoestradiolinthefemalerathypothalamus |