Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status
Abstract Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in...
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doaj-b46362d05214469699a96b8b5866641b2020-12-08T00:11:10ZengNature Publishing GroupScientific Reports2045-23222017-04-017111010.1038/s41598-017-01183-8Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid statusMika Kiyohara0You Lee Son1Kazuyoshi Tsutsui2Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda UniversityLaboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda UniversityLaboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda UniversityAbstract Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty. In contrast, hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was normal, implying further reduction of the inhibitory GnIH had little effect on the phenotypical change. Critically, thyroid hormone suppressed GnIH expression in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to convey the thyroid status. Moreover, the thyroid status highly regulated the chromatin modifications of GnIH promoter, H3acetylation and H3K9tri-methylation. These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development.https://doi.org/10.1038/s41598-017-01183-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mika Kiyohara You Lee Son Kazuyoshi Tsutsui |
spellingShingle |
Mika Kiyohara You Lee Son Kazuyoshi Tsutsui Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status Scientific Reports |
author_facet |
Mika Kiyohara You Lee Son Kazuyoshi Tsutsui |
author_sort |
Mika Kiyohara |
title |
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
title_short |
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
title_full |
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
title_fullStr |
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
title_full_unstemmed |
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
title_sort |
involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-04-01 |
description |
Abstract Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty. In contrast, hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was normal, implying further reduction of the inhibitory GnIH had little effect on the phenotypical change. Critically, thyroid hormone suppressed GnIH expression in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to convey the thyroid status. Moreover, the thyroid status highly regulated the chromatin modifications of GnIH promoter, H3acetylation and H3K9tri-methylation. These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development. |
url |
https://doi.org/10.1038/s41598-017-01183-8 |
work_keys_str_mv |
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