scholarly journals Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

2022 ◽  
Vol 12 ◽  
Author(s):  
Grégoy Y. Bédécarrats ◽  
Charlene Hanlon ◽  
Kazuyoshi Tsutsui

Since its discovery as a novel gonadotropin inhibitory peptide in 2000, the central and peripheral roles played by gonadotropin-inhibiting hormone (GnIH) have been significantly expanded. This is highlighted by the wide distribution of its receptor (GnIH-R) within the brain and throughout multiple peripheral organs and tissues. Furthermore, as GnIH is part of the wider RF-amide peptides family, many orthologues have been characterized across vertebrate species, and due to the promiscuity between ligands and receptors within this family, confusion over the nomenclature and function has arisen. In this review, we intend to first clarify the nomenclature, prevalence, and distribution of the GnIH-Rs, and by reviewing specific localization and ligand availability, we propose an integrative role for GnIH in the coordination of reproductive and metabolic processes. Specifically, we propose that GnIH participates in the central regulation of feed intake while modulating the impact of thyroid hormones and the stress axis to allow active reproduction to proceed depending on the availability of resources. Furthermore, beyond the central nervous system, we also propose a peripheral role for GnIH in the control of glucose and lipid metabolism at the level of the liver, pancreas, and adipose tissue. Taken together, evidence from the literature strongly suggests that, in fact, the inhibitory effect of GnIH on the reproductive axis is based on the integration of environmental cues and internal metabolic status.

Author(s):  
Onder Celik ◽  
Nilufer Celik ◽  
Suleyman Aydin ◽  
Banu Kumbak Aygun ◽  
Esra Tustas Haberal ◽  
...  

AbstractAcylated ghrelin (AG) effect on GnRH secretion is mediated, at least in part, by GH secreta-gogue receptor (GHS-R) which is present in the GnRH neurons. As the acylation is mandatory for binding to GHS-R, unacylated isoform of ghrelin (UAG) action on gonadotropin secretion is likely to be mediated by other receptors or mediators that have not been identified yet. UAG, therefore, may act partially via a GHS-R-independent mechanism and inhibitory impact of UAG on GnRH neurons may be executed via modulation of other neuronal networks. Ghrelin and gonadotropin inhibitory hormone (GnIH), two agonistic peptides, have been known as important regulators of reproductive events. Potential impact of ghrelin on the activity of GnIH neurons is not exactly known. Both GnIH and ghrelin are potent stimulators of food intake and inhibitors of gonadotropin release. By binding G-protein coupled GnIH receptor (GnIH-R), GPR147, which is located in the human gonadotropes and GnRh neurons, GnIH exerts an inhibitory effect on both GnRH neurons and the gonadotropes. The GnIH-GPR147 system receives information regarding the status of energy reservoir of body from circulating peptides and then transfers them to the kisspeptin-GnIH-GnRH network. Due to wide distribution of this network in brain GnIH neurons may project on ghrelin neurons in the arcuate nucleus and contribute to the regulation of UAG’s central effects or vice versa. Together, the unidentified ghrelin receptor in the hypothalamus and hypophysis may be GnIH-R. Therefore, it is reasonable that ghrelin may act on both hypothalamus and hypophysis via GnIH-GPR147 system to block gonadotropin synthesis and secretion.


Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2953-2965 ◽  
Author(s):  
Silvia León ◽  
David García-Galiano ◽  
Francisco Ruiz-Pino ◽  
Alexia Barroso ◽  
María Manfredi-Lozano ◽  
...  

RF-amide-related peptide-3 (RFRP-3), the mammalian ortholog of the avian gonadotropin-inhibiting hormone (GnIH), operates via the NPFF1 receptor (NPFF1R) to repress the reproductive axis, therefore acting as counterpart of the excitatory RF-amide peptide, kisspeptin (ligand of Gpr54). In addition, RFRP-3 modulates feeding and might contribute to the integrative control of energy homeostasis and reproduction. Yet, the experimental evidence supporting these putative functions is mostly indirect, and the physiological roles of RFRP-3 remain debatable and obscured by the lack of proper analytical tools and models. To circumvent these limitations, we characterize herein the first mouse line with constitutive inactivation of NPFF1R. Ablation of NPFF1R did not compromise fertility; rather, litters from NPFF1R null mice were larger than those from wild-type animals. Pubertal timing was not altered in NPFF1R deficient mice; yet, pre-pubertal knockout (KO) males displayed elevated LH levels, which normalized after puberty. Adult NPFF1R null male mice showed increased Kiss1 expression in the hypothalamic arcuate nucleus, higher serum FSH levels, and enhanced LH responses to GnRH. However, genetic elimination of NPFF1R was unable to reverse the state of hypogonadism caused by the lack of kisspeptin signaling, as revealed by double NPFF1R/Gpr54 KO mice. NPFF1R null mice displayed altered feedback responses to gonadal hormone withdrawal. In addition, metabolic challenges causing gonadotropin suppression, such as short-term fasting and high-fat diet, were less effective in dampening LH secretion in NPFF1R-deficient male mice, suggesting that absence of this inhibitory pathway partially prevented gonadotropin suppression by metabolic stress. Our data are the first to document the impact of elimination of GnIH signaling on reproductive parameters and their modulation by metabolic challenges. Whereas, in keeping with its inhibitory role, the NPFF1R pathway seems dispensable for preserved puberty and fertility, our results surface different alterations due to the lack of GnIH signaling that prominently include changes in the sensitivity to fasting- and obesity-associated hypogonadotropism.


2020 ◽  
Vol 14 (2) ◽  
pp. 141-152
Author(s):  
Xialing Sun ◽  
Rui Zhang ◽  
Xue Chen ◽  
Pengpeng Li ◽  
Jin Guo

Background: The sustainable development of the building industry has drawn increasing attention around the world. Nanomaterials and nanotechnology play an important role in the processes of energy saving and reducing consumption in the building industry. Nanotechnology patents provide key technological support for the green development of the building industry. Based on patent data in China, this paper quantitatively analyzed the application of nanotechnology patents in the building industry and the time trend, regional differences, and evolution of China's nano-patent applications in the building field. Methods: In this study, the environmental total factor productivity of the building industry considering carbon constraints was determined and then used as the dependent variable to measure the green development of the building industry. On this basis, a panel data regression model was constructed to determine the impact of nano-patents on the green development of the building industry. Results: Nanotechnology patents in the building industry can significantly improve total factor productivity. From the perspective of patent composition, technology-based patents that focus on substantial innovation can significantly promote the green development of the building industry, whereas strategic patents show a significant inhibitory effect. Regionally, the western region of China has the advantage of being less developed and thus more efficient than the central and eastern regions in the application of new nano-products. Finally, the research also showed a significant lag in the application of China's nanotechnology patents and low implementation efficiency. Conclusion: Nano patents can promote green development in the building industry, but there is room for improvement in the speed with which laboratory inventions are transformed into building engineering applications.


Water ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 77
Author(s):  
Cristina Adochite ◽  
Luminita Andronic

In the last years, nanoparticles such as TiO2, ZnO, NiO, CuO and Fe2O3 were mainly used in wastewater applications. In addition to the positive aspects concerning using nanoparticles in the advanced oxidation process of wastewater containing pollutants, the impact of these nanoparticles on the environment must also be investigated. The toxicity of nanoparticles is generally investigated by the nanomaterials’ effect on green algae, especially on Chlorella vulgaris. In this review, several aspects are reviewed: the Chlorella vulgaris culture monitoring and growth parameters, the effect of different nanoparticles on Chlorella vulgaris, the toxicity of photocatalyst nanoparticles, and the mechanism of photocatalyst during oxidative stress on the photosynthetic mechanism of Chlorella vulgaris. The Bold basal medium (BBM) is generally recognized as an excellent standard cultivation medium for Chlorella vulgaris in the known environmental conditions such as temperature in the range 20–30 °C and light intensity of around 150 μE·m2·s−1 under a 16/8 h light/dark cycle. The nanoparticles synthesis methods influence the particle size, morphology, density, surface area to generate growth inhibition and further algal deaths at the nanoparticle-dependent concentration. Moreover, the results revealed that nanoparticles caused a more potent inhibitory effect on microalgal growth and severely disrupted algal cells’ membranes.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.


Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun-Hung Kuang ◽  
Yu-Fu Fang ◽  
Shau-Ching Lin ◽  
Shin-Fu Tsai ◽  
Zhi-Wei Yang ◽  
...  

Abstract Background The impact of climate change on insect resistance genes is elusive. Hence, we investigated the responses of rice near-isogenic lines (NILs) that carry resistance genes against brown planthopper (BPH) under different environmental conditions. Results We tested these NILs under three environmental settings (the atmospheric temperature with corresponding carbon dioxide at the ambient, year 2050 and year 2100) based on the Intergovernmental Panel on Climate Change prediction. Comparing between different environments, two of nine NILs that carried a single BPH-resistant gene maintained their resistance under the environmental changes, whereas two of three NILs showed gene pyramiding with two maintained BPH resistance genes despite the environmental changes. In addition, two NILs (NIL-BPH17 and NIL-BPH20) were examined in their antibiosis and antixenosis effects under these environmental changes. BPH showed different responses to these two NILs, where the inhibitory effect of NIL-BPH17 on the BPH growth and development was unaffected, while NIL-BPH20 may have lost its resistance during the environmental changes. Conclusion Our results indicate that BPH resistance genes could be affected by climate change. NIL-BPH17 has a strong inhibitory effect on BPH feeding on phloem and would be unaffected by environmental changes, while NIL-BPH20 would lose its ability during the environmental changes.


2021 ◽  
Vol 13 (5) ◽  
pp. 2730
Author(s):  
Yuan Zhao ◽  
Tian Zhang ◽  
Ting Wu ◽  
Shujing Xu ◽  
Shuwang Yang

Technological progress has always been regarded as an important factor affecting haze pollution. A large number of academic studies have focused on the effect of technological progress on haze pollution, but there are few discussions on the effects of technological progress from different sources. In view of this, a dynamic panel model is constructed, and a systematic generalized method of moments (GMM) method is applied to empirically test the overall impact of technological progress from different sources on haze pollution and the regional heterogeneity of the impact. The results show that the overall and regional impact of technological progress from different sources on haze pollution is entirely different. Among them, for the whole country, independent innovation has a significant inhibitory effect on haze pollution, and technology introduction has aggravated haze pollution to a certain extent. At the regional level, all types of technological progress in the east can effectively reduce haze, the central region having haze reduction results consistent with the overall national level, and in the west, independent innovation and direct introduction can effectively reduce haze, while reverse technology spillover is ineffective. Therefore, policy recommendations such as improving the ability of independent innovation, improving the quality of technology introduction, and coordinating regional technology against haze are put forward.


2008 ◽  
Vol 52 (8) ◽  
pp. 2882-2889 ◽  
Author(s):  
Metodi V. Stankov ◽  
Reinhold E. Schmidt ◽  
Georg M. N. Behrens

ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.


1993 ◽  
Vol 137 (2) ◽  
pp. 247-NP ◽  
Author(s):  
H. F. Urbanski ◽  
M. M. Fahy ◽  
P. M. Collins

ABSTRACT The influence of excitatory amino acids (EAAs) on reproductive neuroendocrine function was investigated in adult male Syrian hamsters of the LSH/Ss Lak strain. Before the study, the animals were maintained in a sexually regressed condition, under short days (SD) and subsequently were either transferred to long days (LD) or kept under SD, for a further 4 weeks. In the former group, photostimulation produced a predictable elevation in the hypophysial contents and serum concentrations of FSH and LH. This was accompanied by an increase in testicular size, an elevation in serum testosterone levels and an increase in spermatogenic activity; the SD hamsters remained sexually quiescent throughout the study. In contrast, SD hamsters that were given daily injections of the EAA agonist, N-methyl-d,l-aspartate (NMA: 50 mg/kg body weight, s.c.), showed stimulatory responses that were generally even more pronounced than those shown by the LD group. Surprisingly, an identical NMA treatment paradigm failed to cause a similar activation of the reproductive axis in LD hamsters that were given daily afternoon injections of melatonin (25 μg, s.c), even though the inhibitory effect of this melatonin treatment is generally regarded as being comparable with that produced by exposure to SD. Although EAAs can acutely stimulate the neurocircuitry that controls LH-releasing hormone secretion, the present findings suggest that EAAs might also exert a long-term stimulatory action by acting further upstream in the photoneuroendocrine pathway. Journal of Endocrinology (1993) 137, 247–252


2009 ◽  
Vol 207 (1) ◽  
pp. 39-49 ◽  
Author(s):  
Nicoletta Casartelli ◽  
Florence Guivel-Benhassine ◽  
Romain Bouziat ◽  
Samantha Brandler ◽  
Olivier Schwartz ◽  
...  

The cytidine deaminase APOBEC3G (A3G) enzyme exerts an intrinsic anti–human immunodeficiency virus (HIV) defense by introducing lethal G-to-A hypermutations in the viral genome. The HIV-1 viral infectivity factor (Vif) protein triggers degradation of A3G and counteracts this antiviral effect. The impact of A3G on the adaptive cellular immune response has not been characterized. We examined whether A3G-edited defective viruses, which are known to express truncated or misfolded viral proteins, activate HIV-1–specific (HS) CD8+ cytotoxic T lymphocytes (CTLs). To this end, we compared the immunogenicity of cells infected with wild-type or Vif-deleted viruses in the presence or absence of the cytidine deaminase. The inhibitory effect of A3G on HIV replication was associated with a strong activation of cocultivated HS-CTLs. CTL activation was particularly marked with Vif-deleted HIV and with viruses harboring A3G. Enzymatically inactive A3G mutants failed to enhance CTL activation. We also engineered proviruses bearing premature stop codons in their genome as scars of A3G editing. These viruses were not infectious but potently activated HS-CTLs. Therefore, the pool of defective viruses generated by A3G represents an underestimated source of viral antigens. Our results reveal a novel function for A3G, acting not only as an intrinsic antiviral factor but also as an inducer of the adaptive immune system.


Sign in / Sign up

Export Citation Format

Share Document