Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status

Mika Kiyohara, You Lee Son, Kazuyoshi Tsutsui

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    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.

    Original languageEnglish
    Article number1042
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 2017 Dec 1

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    Gonadotropins
    Thyroid Gland
    Hormones
    Hypothyroidism
    Hypothalamus
    Delayed Puberty
    Thyroid Hormone Receptors
    Hyperthyroidism
    Puberty
    Thyroid Hormones
    Knockout Mice
    Methylation
    Chromatin
    Neurons

    ASJC Scopus subject areas

    • General

    Cite this

    Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status. / Kiyohara, Mika; Son, You Lee; Tsutsui, Kazuyoshi.

    In: Scientific Reports, Vol. 7, No. 1, 1042, 01.12.2017.

    Research output: Contribution to journalArticle

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