• Development and Reproduction
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• v.22 no.2
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• pp.119-132
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• 2018

GnRH (gonadotropin-releasing hormone) is a supreme hormone regulating reproductive activity in most animals. The sequences of amino acid and nucleic acid of GnRH reported up to now are examined from the evolutionary framework of Chordata. All identified GnRH are classified into GnRH1, GnRH2, or GnRH3. In all three forms of GnRH both N-terminal and C-terminal are conserved, which allows for effective binding to their receptors. The three amino acids in the middle of GnRH1 sequence have altered diversely from the primitive Chordata, which is indicative of the adaptation process to the ambient environment. GnRH2 and GnRH3 sequences are well conserved. There are more diverse modifications in the nucleic acids than in amino acid sequence of GnRH1. These variations can result from meiosis, mutation, or epigenetics and indicate that GnRH is the product of natural selection.

• Fisheries and Aquatic Sciences
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• v.27 no.6
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• pp.366-378
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• 2024

Application of commercial hormone failed to promote breeding in certain Pangasius species due to the differences of gonadotropin-releasing hormone specific peptide with species-specific bioactivities. Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide in the reproductive system that plays a crucial role in the regulation of reproductive processes. This study was performed to determine and analyse the GnRH genes from commercially important Pangasius sp., Pangasianodon hypophthalmus and Pangasius nasutus. The GnRH1 and GnRH2 genes were amplified and cloned into TOPO vector, followed by phylogenetic analysis of a complete open reading frame (ORF) of GnRH genes. The GnRH1 and GnRH2 genes of P. hypophthalmus and P. nasutus were detected at 300 bp and 360 bp, encoded for 81 and 87 amino acids, respectively. Amino acid sequence identities revealed high homology of P. hypophthalmus and P. nasutus GnRH1 and GnRH2 genes in comparison with other fish and vertebrates. Phylogenetic tree showed that fish from various families were aggregated into a group of the same order due to their highest identity similarities. It revealed that the vertebrate formed clusters and are grouped according to their GnRH decapeptide and GnRH-associated peptide (GAP) region, indicating a close relationship among GnRH decapeptide and GAP in different vertebrate species.

• Development and Reproduction
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• v.28 no.1
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• pp.1-12
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• 2024

Gonadotropin-releasing hormone (GnRH), a critical hormone produced in the hypothalamus, is essential for regulating reproductive processes. It has also been demonstrated the presence of GnRH and its receptors (GnRHR) in ovarian and uterine tissues, but little was known about the regulation mechanism of their expression in these organs and ovarian aging. Therefore, the aim of this study was to investigate the expression of GnRHR in the ovary and uterus of mice, particularly after high-dose gonadotropin treatments and in relation to aging. Quantitative real-time-PCR (qRT-PCR) revealed that pituitary gland had the highest GnRHR expression in both young and aged mice. In addition, liver expression was higher in young mice, whereas thymus expression was higher in aged mice. GnRHR mRNA was present in the ovaries of both young and aged mice but nearly undetectable in the uterus of aged mice. We next examined the expression of GnRHR in the ovary and uterus in response to high-dose administration of pregnant mare serum gonadotropin (PMSG). After PMSG administration, GnRH mRNA levels were significantly decreased in the ovary but increased in the uterus. The expression of GnRH mRNA in these organs showed opposite trends to that of GnRHR expression. These results suggest the involvement of GnRH in age-related reproductive decline and the potential effects of high-dose gonadotropin treatments on reproductive organ function.

• Fisheries and Aquatic Sciences
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• v.14 no.4
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• pp.379-388
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• 2011

The mechanism by which gonadotropin-releasing hormone (GnRH) and dopamine (DA) control gonadotropin (GTH) release was studied in male and female rainbow trout using cultured pituitary cells obtained at different reproductive stages. The mechanisms of follicle-stimulating hormone (FSH) release by GnRH and DA could not be determined yet. However, basal and salmon-type GnRH (sGnRH)- or chicken-II-type GnRH (cGnRH-II)- induced luteinizing hormone (LH) release increased with gonadal maturation in both sexes. LH release activity was higher after sGnRH stimulation than cGnRH-II stimulation at maturing stages in both sexes. The GnRH antagonist ([Ac-3, 4-dehydro-$Pro^1$, D-p-F-$Phe^2$, D-$Trp^{3,6}$] GnRH) suppressed LH release by sGnRH stimulation in a dose-dependent manner, although the effect was weak in maturing fish. The role of DA as a GTH-release inhibitory factor differs during the reproductive cycle: the inhibition of sGnRH-stimulated LH release by DA was stronger in immature fish than in maturing, ovulating, or spermiated fish. DA did not completely inhibit sGnRH-stimulated LH release, and DA alone did not alter basal LH release. Relatively high doses ($10^{-6}$ or $10^{-5}M$) of domperidone (DOM, a DA D2 antagonist) increased LH release, which did not change with reproductive stage in either sex. The potency of DOM to enhance sGnRH-stimulated LH release was higher in maturing and ovulated fish than in immature fish. These data suggest that LH release from the pituitary gland is controlled by dual neuroendocrine mechanisms by GnRH and DA in rainbow trout, as has been reported in other teleosts. The mechanism of control of FSH release, however, remains unknown.

• Animal cells and systems
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• v.5 no.3
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• pp.217-224
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• 2001

The present study examines the expression and regulation of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R) mRNA levels during mouse ovarian development. A fully processed, mature GnRH mRNA together with intron-containing primary transcripts was expressed in the immature mouse ovary as determined by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). The size of ovarian GnRH mRNA was similar to that of hypothalamus, but its amount was much lower than that in the hypothalamus. Quantitative RT-PCR procedure also revealed the expression of GnRH-R mRNA in the ovary, but the estimated amount was a thousand-fold lower than that in the pituitary gland. We also examined the regulation of ovarian GnRH and GnRH-R mRNA levels during the follicular development induced by pregnant mare's serum gonadotropin (PMSG) and/or human chorionic gonadotropin (hCG). Ovarian luteinizing hormone receptor (LH-R) mRNA was abruptly increased st 48 h after the PMSG administration and rapidly decreased to the basal level thereafter. Ovarian GnRH mRNA level was slightly decreased at 48 h after the PMSG administration, and then returned to the basal value. GnRH-R mRNA level began to increase at 24 h after the PMSG treatment, decreased below the uninduced basal level at 48 h, and gradually increased thereafter. HCG administration did not alter ovarian GnRH mRNA level, while it blocked the PMSG-induced increase in GnRH mRNA level. Taken together, the present study demonstrates that the expression of GnRH and GnRH-R mRNA are regulated by gonadotropin during follicular development, suggesting possible intragonadal paracrine roles of GnRH and GnRH-R in the mouse ovarian development.

• Animal cells and systems
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• v.11 no.2
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• pp.93-98
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• 2007

Gonadotropin-releasing hormone (GnRH), synthesized in the hypothalamus, plays a pivotal role in the regulation of vertebrate reproduction. Since molecular isoforms of GnRH and their receptors (GnRHR) have been isolated in a broad range of vertebrate species, GnRH and GnRHR provide an excellent model for understanding the molecular co-evolution of a peptide ligand-receptor pair. Vertebrate species possess multiple forms of GnRH, which have been created through evolutionary mechanisms such as gene/chromosome duplication, gene deletion and modification. Similar to GnRHs, GnRH receptors (GnRHR) have also been diversified evolutionarily. Comparative ligand-receptor interaction studies for non-mammalian and mammalian GnRHRs combined with mutational mapping studies of GnRHRs have aided the identification of domains or motifs responsible for ligand binding and receptor activation. Here we discuss the molecular basis of GnRH-GnRHR co-evolution, particularly the structure-function relationship regarding ligand selectivity and signal transduction of mammalian and non-mammalian GnRHRs.

• Molecules and Cells
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• v.25 no.1
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• pp.91-98
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• 2008

The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

• Clinical and Experimental Pediatrics
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• v.53 no.9
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• pp.845-851
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• 2010

Purpose: Recombinant human growth hormone (rhGH) has been widely used to treat short stature. However, there are some concerns that growth hormone treatment may induce skeletal maturation and early onset of puberty. In this study, we investigated whether rhGH can directly affect the neuronal activities of of gonadotropin-releasing hormone (GnRH). Methods: We performed brain slice gramicidin-perforated current clamp recording to examine the direct membrane effects of rhGH on GnRH neurons, and a whole-cell voltage-clamp recording to examine the effects of rhGH on spontaneous postsynaptic events and holding currents in immature (postnatal days 13-21) and adult (postnatal days 42-73) mice. Results: In immature mice, all 5 GnRH neurons recorded in gramicidin-perforated current clamp mode showed no membrane potential changes on application of rhGH (0.4, $1{\mu}g/mL$). In adult GnRH neurons, 7 (78%) of 9 neurons tested showed no response to rhGH ($0.2-1{\mu}g/mL$) and 2 neurons showed slight depolarization. In 9 (90%) of 10 immature neurons tested, rhGH did not induce any membrane holding current changes or spontaneous postsynaptic currents (sPSCs). There was no change in sPSCs and holding current in 4 of 5 adult GnRH neurons. Conclusion: These findings demonstrate that rhGH does not directly affect the GnRH neuronal activities in our experimental model.

• Korean Journal of Veterinary Research
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• v.21 no.1
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• pp.59-64
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• 1981

Holstein-Friesian cows(n=284) were given $100{\mu}g$ of gonadotropin-releasing hormone(GnRH) or saline solution by intramuscular injection at 10 to 22 days after parturition, and were investigated their reproductive performance and frequency of ovarian cysts. Among them 28 cystic cows were injected with $150{\mu}g$ of GnRH intramuscularly and examined the recovery rate. The results obtained in this study were summarized as follows: 1. The interval from calving to 1st ovulation was reduced from 28.2 days in controls to 16.5 days for cows given GnRH (p<0.01). 2. The intervals from calving to 1st estrus and from calving to conception were extended significantly in control group (p<0.05). 3. Inseminations per conception and conception rate at 1st insemination did not reveal difference between two groups. 4. Frequency of ovarian cysts was reduced from 14.0% in control to 4.20% for cows given GnRH (p<0.05). 5. Of the 28 cystic cows receiving $150{\mu}g$ of GnRH, 23(82.1%) responded to 1st treatment and returned to estrus $24.2{\pm}4.3$ days after treatment. 6. These data provide evidence for reduction in infertility and reproductive disorders in early postpartum dairy cows given GnRH as a prophylactic.

• Journal of Aquaculture
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• v.9 no.1
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• pp.3-10
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• 1996

Ovulation of maturing female yellow puffer, Takifugu obscrus, was induced by using single injection of human chorionic gonadotropin (HCG) or gonadotropin releasing hormone-analogue (GnRH-A) $des-Gly^{10}[D-Ala^6]$ GnRH-ethylamide plus pimozide. The response was evaluated using the fertilization and embryo-formation rate after insemination and the gonadotropin (GTH) level in blood plasma using radioimmunoassay. In the fertilization and embryo-formation, maximal effects were recorded by using 1,000 IU/kg HCG or $10\;{mu}g/kg$ GnRH-A plus 5 mg/kr pimozide. Pimozide (1, 5 mg/kg) or GnRH-A treatment alone was not effective in elevation of GTH level, however combinations of these treatments were particularly effective. Injection of dopamine blocked the rapid elevation of plasma GTH levels of blood. These data suggest that yellow puffer secrete GnRH and gonadotropin-releasing-inhibiting factor during the spawning or the other period.