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Review: evolution of GnIH and related peptides structure and function in the chordates.

ABSTRACT: Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus and inhibit pituitary gonadotropin secretion. However, the function and structure of GnIH peptides are diverse in fish. Goldfish GnIHs possessing a C-terminal LPXRF-amide motif have both stimulatory and inhibitory effects on gonadotropin synthesis or release. The C-terminal sequence of grass puffer and medaka GnIHs are MPQRF-amide. To investigate the evolutionary origin of GnIH and its ancestral structure and function, we searched for GnIH in agnathans, the most ancient lineage of vertebrates. We identified GnIH precursor gene and mature GnIH peptides with C-terminal QPQRF-amide or RPQRF-amide from the brain of sea lamprey. Lamprey GnIH fibers were in close proximity to GnRH-III neurons. Further, one of lamprey GnIHs stimulated the expression of lamprey GnRH-III peptide in the hypothalamus and gonadotropic hormone ? mRNA expression in the pituitary. We further identified the ancestral form of GnIH, which had a C-terminal RPQRF-amide, and its receptors in amphioxus, the most basal chordate species. The amphioxus GnIH inhibited cAMP signaling in vitro. In sum, the original forms of GnIH may date back to the time of the emergence of early chordates. GnIH peptides may have had various C-terminal structures slightly different from LPXRF-amide in basal chordates, which had stimulatory and/or inhibitory functions on reproduction. The C-terminal LPXRF-amide structure and its inhibitory function on reproduction may be selected in later-evolved vertebrates, such as birds and mammals.

SUBMITTER: Osugi T

PROVIDER: S-EPMC4133751 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Review: evolution of GnIH and related peptides structure and function in the chordates.

Osugi Tomohiro T Ubuka Takayoshi T Tsutsui Kazuyoshi K

Frontiers in neuroscience 20140815

Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus a ...[more]

PMID: 25177268

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Project description:It is essential to discover novel neuropeptides that regulate the functions of pituitary, brain and peripheral secretory glands for the progress of neuroendocrinology. Gonadotropin-releasing hormone (GnRH), a hypothalamic neuropeptide stimulating gonadotropin release was isolated and its structure was determined by Schally's and Guillemin's groups at the beginning of the 1970s. It was subsequently shown that GnRH is highly conserved among vertebrates. GnRH was assumed the sole hypothalamic neuropeptide that regulates gonadotropin release in vertebrates based on extensive studies of GnRH over the following three decades. However, in 2000, Tsutsui's group isolated and determined the structure of a novel hypothalamic neuropeptide, which inhibits gonadotropin release, in quail, an avian species, and named it gonadotropin-inhibitory hormone (GnIH). Following studies by Tsutsui's group demonstrated that GnIH is highly conserved among vertebrates, from humans to agnathans, and acts as a key neuropeptide inhibiting reproduction. Intensive research on GnIH demonstrated that GnIH inhibits gonadotropin synthesis and release by acting on gonadotropes and GnRH neurons via GPR147 in birds and mammals. Fish GnIH also regulates gonadotropin release according to its reproductive condition, indicating the conserved role of GnIH in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. Therefore, we can now say that GnRH is not the only hypothalamic neuropeptide controlling vertebrate reproduction. In addition, recent studies by Tsutsui's group demonstrated that GnIH acts in the brain to regulate behaviors, including reproductive behavior. The 18 years of GnIH research with leading laboratories in the world have significantly advanced our knowledge of the neuroendocrine control mechanism of reproductive physiology and behavior as well as interactions of the HPG, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes. This review describes how GnIH was discovered and GnIH research progressed in this new research era of reproductive neuroendocrinology.

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Review: evolution of GnIH and related peptides structure and function in the chordates.

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Review: evolution of GnIH and related peptides structure and function in the chordates.

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