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Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice
BACKGROUND: Sex differences in pituitary growth hormone (GH) are well documented and coordinate maturation and growth. GH and its receptor are also produced in the brain where they may impact cognitive function and synaptic plasticity, and estradiol produces Gh sex differences in rat hippocampus. In...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434521/ https://www.ncbi.nlm.nih.gov/pubmed/25987976 http://dx.doi.org/10.1186/s13293-015-0026-x |
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author | Quinnies, Kayla M Bonthuis, Paul J Harris, Erin P Shetty, Savera RJ Rissman, Emilie F |
author_facet | Quinnies, Kayla M Bonthuis, Paul J Harris, Erin P Shetty, Savera RJ Rissman, Emilie F |
author_sort | Quinnies, Kayla M |
collection | PubMed |
description | BACKGROUND: Sex differences in pituitary growth hormone (GH) are well documented and coordinate maturation and growth. GH and its receptor are also produced in the brain where they may impact cognitive function and synaptic plasticity, and estradiol produces Gh sex differences in rat hippocampus. In mice, circulating estradiol increases Gh mRNA in female but not in male medial preoptic area (mPOA); therefore, additional factors regulate sexually dimorphic Gh expression in the brain. Thus, we hypothesized that sex chromosomes interact with estradiol to promote sex differences in GH. Here, we assessed the contributions of both estradiol and sex chromosome complement on Gh mRNA levels in three large brain regions: the hippocampus, hypothalamus, and cerebellum. METHODS: We used the four core genotypes (FCG) mice, which uncouple effects of sex chromosomes and gonadal sex. The FCG model has a deletion of the sex-determining region on the Y chromosome (Sry) and transgenic insertion of Sry on an autosome. Adult FCG mice were gonadectomized and given either a blank Silastic implant or an implant containing 17β-estradiol. Significant differences in GH protein and mRNA were attributed to estradiol replacement, gonadal sex, sex chromosome complement, and their interactions, which were assessed by ANOVA and planned comparisons. RESULTS: Estradiol increased Gh mRNA in the cerebellum and hippocampus, regardless of sex chromosome complement or gonadal sex. In contrast, in the hypothalamus, females had higher Gh mRNA than males, and XY females had more Gh mRNA than XY males and XX females. This same pattern was observed for GH protein. Because the differences in Gh mRNA in the hypothalamus did not replicate prior studies using other mouse models and tissue from mPOA or arcuate nucleus, we examined GH protein in the arcuate, a subdivision of the hypothalamus. Like the previous reports, and in contrast to the entire hypothalamus, a sex chromosome complement effect showed that XX mice had more GH than XY in the arcuate. CONCLUSIONS: Sex chromosome complement regulates GH in some but not all brain areas, and within the hypothalamus, sex chromosomes have cell-specific actions on GH. Thus, sex chromosome complement and estradiol both contribute to GH sex differences in the brain. |
format | Online Article Text |
id | pubmed-4434521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44345212015-05-19 Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice Quinnies, Kayla M Bonthuis, Paul J Harris, Erin P Shetty, Savera RJ Rissman, Emilie F Biol Sex Differ Research BACKGROUND: Sex differences in pituitary growth hormone (GH) are well documented and coordinate maturation and growth. GH and its receptor are also produced in the brain where they may impact cognitive function and synaptic plasticity, and estradiol produces Gh sex differences in rat hippocampus. In mice, circulating estradiol increases Gh mRNA in female but not in male medial preoptic area (mPOA); therefore, additional factors regulate sexually dimorphic Gh expression in the brain. Thus, we hypothesized that sex chromosomes interact with estradiol to promote sex differences in GH. Here, we assessed the contributions of both estradiol and sex chromosome complement on Gh mRNA levels in three large brain regions: the hippocampus, hypothalamus, and cerebellum. METHODS: We used the four core genotypes (FCG) mice, which uncouple effects of sex chromosomes and gonadal sex. The FCG model has a deletion of the sex-determining region on the Y chromosome (Sry) and transgenic insertion of Sry on an autosome. Adult FCG mice were gonadectomized and given either a blank Silastic implant or an implant containing 17β-estradiol. Significant differences in GH protein and mRNA were attributed to estradiol replacement, gonadal sex, sex chromosome complement, and their interactions, which were assessed by ANOVA and planned comparisons. RESULTS: Estradiol increased Gh mRNA in the cerebellum and hippocampus, regardless of sex chromosome complement or gonadal sex. In contrast, in the hypothalamus, females had higher Gh mRNA than males, and XY females had more Gh mRNA than XY males and XX females. This same pattern was observed for GH protein. Because the differences in Gh mRNA in the hypothalamus did not replicate prior studies using other mouse models and tissue from mPOA or arcuate nucleus, we examined GH protein in the arcuate, a subdivision of the hypothalamus. Like the previous reports, and in contrast to the entire hypothalamus, a sex chromosome complement effect showed that XX mice had more GH than XY in the arcuate. CONCLUSIONS: Sex chromosome complement regulates GH in some but not all brain areas, and within the hypothalamus, sex chromosomes have cell-specific actions on GH. Thus, sex chromosome complement and estradiol both contribute to GH sex differences in the brain. BioMed Central 2015-04-28 /pmc/articles/PMC4434521/ /pubmed/25987976 http://dx.doi.org/10.1186/s13293-015-0026-x Text en © Quinnies et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Quinnies, Kayla M Bonthuis, Paul J Harris, Erin P Shetty, Savera RJ Rissman, Emilie F Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title | Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title_full | Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title_fullStr | Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title_full_unstemmed | Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title_short | Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
title_sort | neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434521/ https://www.ncbi.nlm.nih.gov/pubmed/25987976 http://dx.doi.org/10.1186/s13293-015-0026-x |
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