Advancing reproductive neuroendocrinology through research on the regulation of GnIH and on its diverse actions on reproductive physiology and behavior

Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Ukena, Kazuyoshi

doi:10.1016/j.yfrne.2021.100955

Cited by 14 publications

(8 citation statements)

References 184 publications

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“…It has been well demonstrated that both LPXRFa and Kiss peptides play a key role in the regulation of reproductive axis at multiple levels in vertebrates, including fish. However, the link between energy balance and reproduction via these two neuropeptides is still largely unknown (2,26,27,52,60). In the current study, we evaluated the effects of nutritional status on the transcript levels of the elements of both…”

Section: Discussionmentioning

confidence: 99%

“…In 2000, a novel hypothalamic neuropeptide was discovered in the Japanese quail, and was termed gonadotropin-inhibitory hormone (GnIH) based on its ability to inhibit gonadotropin release (1). Subsequently, its homologues have been identified in various vertebrates, including fish, amphibians, reptiles, birds and mammals (2)(3)(4). GnIH is also called LPXRFa in teleosts or RFamide-related peptide (RFRP) in mammals, and its precursor encompasses two, three or four putative/mature peptides depending on the species, which generally possess a common C-terminal LPXRFamide (X = L or Q) motif (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

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Food deprivation differentially modulates gene expression of LPXRFa and kisspeptin systems in the brain-pituitary axis of half-smooth tongue sole (Cynoglossus semilaevis)

Wang

Cui

et al. 2023

Front. Endocrinol.

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LPXRFa, also known as gonadotropin-inhibitory hormone (GnIH), and kisspeptin (Kiss) are two major hypothalamic peptides that modulate the reproductive axis of vertebrates, including teleosts. However, little information is available regarding the actions of nutritional status on the regulation of these two neuroendocrine systems in fish. Herein, we assessed the effects of starvation and refeeding on the expression of lpxrfa, kiss2 and their receptors (lpxrfa-r and kiss2r respectively) at the brain-pituitary level of half-smooth tongue sole (Cynoglossus semilaevis). Food deprivation for 4 weeks induced a rise in brain lpxrfa as well as brain and pituitary lpxrfa-r mRNA levels, and refeeding restored brain lpxrfa and lpxrfa-r expression back to normal. However, pituitary lpxrfa-r mRNA levels still remained high after 1 week of refeeding. Neither lpxrfa nor kiss2 transcripts in the pituitary were altered by fasting, but their mRNA levels increased significantly after 1 week of refeeding, and declined back to the control levels after 2 weeks of refeeding. None of brain kiss2 and kiss2r along with pituitary kiss2r transcripts were modified by the nutritional status. In summary, our results revealed an interaction between energy status and the elements of LPXRFa and Kiss systems in the brain-pituitary axis of half-smooth tongue sole. Food deprivation and refeeding differentially regulated the two systems, which provided additional evidence for the involvement of the LPXRFa and Kiss systems in the regulation of reproduction by energy balance in non-mammalian species.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Food deprivation differentially modulates gene expression of LPXRFa and kisspeptin systems in the brain-pituitary axis of half-smooth tongue sole (Cynoglossus semilaevis)

Wang

Cui

et al. 2023

Front. Endocrinol.

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“…Universally throughout the animal kingdom, energy deficits inhibit the reproductive axis, which demonstrates that reproduction is acutely sensitive to fuel availability. GnIH is well known for its crucial role in the regulation of the reproductive axis [ 12 , 18 , 19 , 20 ], but in light of accumulating data, it has emerged as a novel orexigenic neuropeptide that affects feeding and is potentially involved in energy metabolism [ 14 , 16 , 21 , 22 ]. However, the relationship between GnIH in reproduction and energy metabolism has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Possible Role of GnIH as a Novel Link between Hyperphagia-Induced Obesity-Related Metabolic Derangements and Hypogonadism in Male Mice

Luo

Chen

Song

et al. 2022

IJMS

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Gonadotropin-inhibitory hormone (GnIH) is a reproductive inhibitor and an endogenous orexigenic neuropeptide that may be involved in energy homeostasis and reproduction. However, whether GnIH is a molecular signal link of metabolism and the reproductive system, and thus, regulates reproductive activity as a function of the energy state, is still unknown. In the present study, we investigated the involvement of GnIH in glycolipid metabolism and reproduction in vivo, and in the coupling between these two processes in the testis level. Our results showed that chronic intraperitoneal injection of GnIH into male mice not only increased food intake and altered meal microstructure but also significantly elevated body mass due to the increased mass of liver and epididymal white adipose tissue (eWAT), despite the loss of testicular weight. Furthermore, chronic intraperitoneal administration of GnIH to male mice resulted in obesity-related glycolipid metabolic derangements, showing hyperlipidemia, hyperglycemia, glucose intolerance, and insulin resistance through changes in the expression of glucose and lipid metabolism-related genes in the pancreas and eWAT, respectively. Interestingly, the expression of GnIH and GPR147 was markedly increased in the testis of mice under conditions of energy imbalance, such as fasting, acute hypoglycemia, and hyperglycemia. In addition, chronic GnIH injection markedly inhibited glucose and lipid metabolism of mice testis while significantly decreasing testosterone synthesis and sperm quality, inducing hypogonadism. These observations indicated that orexigenic GnIH triggers hyperphagia-induced obesity-related metabolic derangements and hypogonadism in male mice, suggesting that GnIH is an emerging candidate for coupling metabolism and fertility by involvement in obesity and metabolic disorder-induced reproductive dysfunction of the testes.

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“…GnIH is a hypothalamic peptide expressed in dorsomedial nucleus of hypothalamus (DMH) in most mammals or paraventricular nucleus (PVN) in birds, with fibers extending both to median eminence and to preoptic area to directly inhibit GnRH and gonadotrophin secretion via GnIH receptor (GnIH-R) [20,21,102]. In addition to its effects on reproductive functions, GnIH has been shown to participate in other physiological functions as it is widely distributed in the brain (Fig.…”

Section: Gnihmentioning

confidence: 99%

Effects of undernutrition and low energy availability on reproductive functions and their underlying neuroendocrine mechanisms

et al. 2022

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It has been well established that undernutrition and low energy availability disturb female reproductive functions in humans and many animal species. These reproductive dysfunctions are mainly caused by alterations of some hypothalamic factors, and consequent reduction of gonadotrophin-releasing hormone (GnRH) secretion. Evidence from literature suggests that increased activity of orexigenic factors and decreased activity of anorexigenic/satiety-related factors in undernourished conditions attenuate GnRH secretion in an integrated manner. Likewise, the activity of kisspeptin neurons, which is a potent stimulator of GnRH, is also reduced in undernourished conditions. In addition, it has been suggested that gonadotrophininhibitory hormone, which has anti-GnRH and gonadotrophic effects, may be involved in reproductive dysfunctions under several kinds of stress conditions. It should be remembered that these alterations, i.e., promotion of feeding behavior and temporary suppression of reproductive functions, are induced to prioritize the survival of individual over that of species, and that improvements in metabolic and nutritional conditions should be considered with the highest priority.

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Advancing reproductive neuroendocrinology through research on the regulation of GnIH and on its diverse actions on reproductive physiology and behavior

Cited by 14 publications

References 184 publications

Food deprivation differentially modulates gene expression of LPXRFa and kisspeptin systems in the brain-pituitary axis of half-smooth tongue sole (Cynoglossus semilaevis)

Food deprivation differentially modulates gene expression of LPXRFa and kisspeptin systems in the brain-pituitary axis of half-smooth tongue sole (Cynoglossus semilaevis)

Possible Role of GnIH as a Novel Link between Hyperphagia-Induced Obesity-Related Metabolic Derangements and Hypogonadism in Male Mice

Effects of undernutrition and low energy availability on reproductive functions and their underlying neuroendocrine mechanisms

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