Gonadotropin-inhibitory hormone action in the brain and pituitary

Takayoshi Ubuka, You Lee Son, Yasuko Tobari, Kazuyoshi Tsutsui

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Gonadotropin-inhibitory hormone (GnIH) was first identified in the Japanese quail as a hypothalamic neuropeptide inhibitor of gonadotropin secretion. Subsequent studies have shown that GnIH is present in the brains of birds including songbirds, and mammals including humans. The identified avian and mammalian GnIH peptides universally possess an LPXRFamide (X = L or Q) motif at their C-termini. Mammalian GnIH peptides are also designated as RFamide-related peptides from their structures. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147), which is thought to be coupled to Gαi protein. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN) in birds and the dorsomedial hypothalamic area (DMH) in mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function. GPR147 is expressed in the gonadotropes and GnIH suppresses synthesis and release of gonadotropins. It was further shown in immortalized mouse gonadotrope cell line (LβT2 cells) that GnIH inhibits gonadotropin-releasing hormone (GnRH) induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/PKA-dependent ERK pathway. GnIH neurons also project to GnRH neurons in the preoptic area, and GnRH neurons express GPR147 in birds and mammals. Accordingly, GnIH may inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as directly acting on the gonadotropes. GnIH also inhibits reproductive behavior possibly by acting within the brain. GnIH expression is regulated by a nocturnal hormone melatonin and stress in birds and mammals. Accordingly, GnIH may play a role in translating environmental information to inhibit reproductive physiology and behavior of birds and mammals. Finally, GnIH has therapeutic potential in the treatment of reproductive cycle and hormone-dependent diseases, such as precocious puberty, endometriosis, uterine fibroids, and prostatic and breast cancers.

    Original languageEnglish
    Article numberArticle 148
    JournalFrontiers in Endocrinology
    Volume3
    Issue numberNOV
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Gonadotropins
    Hormones
    Brain
    Birds
    Mammals
    Neurons
    Gonadotropin-Releasing Hormone
    G-Protein-Coupled Receptors
    Reproductive Behavior
    Peptide Hormones
    Paraventricular Hypothalamic Nucleus
    Gonadotropin Receptors
    Precocious Puberty
    Coturnix
    Median Eminence
    Songbirds
    Preoptic Area
    MAP Kinase Signaling System
    Leiomyoma
    Melatonin

    Keywords

    • Gonadotropin-inhibitory hormone
    • Gonadotropin-releasing hormone
    • Gonadotropins
    • Gpr147
    • Melatonin
    • Reproductive behavior
    • Rfamide-related peptide
    • Stress

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism

    Cite this

    Gonadotropin-inhibitory hormone action in the brain and pituitary. / Ubuka, Takayoshi; Son, You Lee; Tobari, Yasuko; Tsutsui, Kazuyoshi.

    In: Frontiers in Endocrinology, Vol. 3, No. NOV, Article 148, 2012.

    Research output: Contribution to journalArticle

    Ubuka, Takayoshi ; Son, You Lee ; Tobari, Yasuko ; Tsutsui, Kazuyoshi. / Gonadotropin-inhibitory hormone action in the brain and pituitary. In: Frontiers in Endocrinology. 2012 ; Vol. 3, No. NOV.
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