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The effect of intracerebroventricular administration of neuropeptide Y on reproductive axis function in the male Wistar rats: Involvement of hypothalamic KiSS1/GPR54 system.

ABSTRACT: Several studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of the hypothalamic-pituitary-gonadal axis in the mammals. Also, kisspeptin is a powerful upstream regulator of gonadotropin-releasing hormone neurons in the hypothalamus. The present study aims to investigate the effects of the intracerebroventricular (ICV) injection of NPY and BIBP3226 (NPY receptor antagonist) on the reproductive axis (either hormonal or behavioral) of the male rats. Furthermore, to see whether NPY signals can be relayed through the pathway of KiSS1/GPR54, the gene expression of these peptides in the arcuate nucleus was measured. The ICV injection of NPY decreased the latencies and increased the frequencies of sexual parameters of the male rats in a significant way. Results obtained from LH and testosterone measurement showed that NPY had a significant increase in comparison with the control group. In this line, BIBP3226 antagonized the stimulative effects of NPY. Furthermore, data from real-time quantitative PCR showed that injection of NPY significantly increased the gene expression of KiSS1 and GPR54, while treatment with BIBP3226 controlled the stimulative effects of NPY on gene expression of KiSS1 and GPR54. Summing up, NPY can exert its impacts on the reproductive axis, this occurs at least partly through affecting KiSS1/GPR54 system.

SUBMITTER: Azizi V

PROVIDER: S-EPMC7597799 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The effect of intracerebroventricular administration of neuropeptide Y on reproductive axis function in the male Wistar rats: Involvement of hypothalamic KiSS1/GPR54 system.

Azizi Vahid V Oryan Shahrbanoo S Khazali Homayuon H

Veterinary research forum : an international quarterly journal 20200915 3

Several studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of the hypothalamic-pituitary-gonadal axis in the mammals. Also, kisspeptin is a powerful upstream regulator of gonadotropin-releasing hormone neurons in the hypothalamus. The present study aims to investigate the effects of the intracerebroventricular (ICV) injection of NPY and BIBP3226 (NPY receptor antagonist) on the reproductive axis (either hormonal or behavioral) of the male rats. Furthermore ...[more]

PMID: 33133462

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Project description:The kisspeptin/Gpr54 signalling pathway plays a critical role in reproduction by stimulating the secretion of gonadotrophin-releasing hormone (GnRH), yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For example, a proportion of female Kiss1(-/-) and Gpr54(-/-) mice exhibit vaginal oestrus, and some male Kiss1(-/-) and Gpr54(-/-) mice exhibit spermatogenesis. To characterise this partial sexual maturation, we examined the vaginal cytology of female Kiss1(-/-) and Gpr54(-/-) mice over time. Almost all mutant mice eventually enter oestrus, and then spontaneously transition from oestrus to dioestrus and back to oestrus again. These transitions are not associated with ovulation, and the frequency of these transitions increases with age. The oestrus exhibited by female Kiss1(-/-) and Gpr54(-/-) mice was disrupted by the administration of the competitive GnRH antagonist acyline, which also resulted in lower uterine weights and, in Kiss1(-/-) mice, lower serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations. Similarly, male Kiss1(-/-) and Gpr54(-/-) mice treated with acyline had smaller testicular sizes and an absence of mature sperm. In addition to examining intact Kiss1(-/-) and Gpr54(-/-) mice, we also assessed the effects of acyline on gonadotrophin concentrations in gonadectomised mice. Gonadectomy resulted in a significant increase in serum FSH concentrations in male Gpr54(-/-) and Kiss1(-/-) mice. Acyline administration to gonadectomised Kiss1(-/-) and Gpr54(-/-) male mice lowered serum FSH and LH concentrations significantly. By contrast to males, gonadectomy did not result in significant gonadotrophin changes in female Kiss1(-/-) and Gpr54(-/-) mice, but acyline administration was followed by a decrease in LH concentrations. These results demonstrate that, although kisspeptin signalling is critical for the high levels of GnRH activity required for normal sexual maturation and for ovulation, Kiss1(-/-) and Gpr54(-/-) mice retain some degree of GnRH activity. This GnRH activity is sufficient to produce significant effects on vaginal cytology and uterine weights in female mice and on spermatogenesis and testicular weights in male mice.

Project description:Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder affecting women of reproductive age. Its aetiology, though yet unclear, is presumed to have an oligogenic basis interacting with environmental factors. Kisspeptins are peptide products of Kiss1 gene that control the hypothalamic pituitary (HPG) axis by acting via G protein-coupled receptor known as GPR54. There is paucity of data on the role of Kiss1 and GPR54 gene in PCOS. We aimed to identify the polymorphisms in Kiss1 and GPR54 genes and explore their association with serum kisspeptin levels among Sri Lankan women with well-characterized PCOS. Consecutive women with PCOS manifesting from adolescence (n=55) and adult controls (n=110) were recruited. Serum kisspeptin and testosterone levels were determined by ELISA method. Whole gene sequencing was performed to identify the polymorphisms in Kiss1 and GPR54 genes. Serum kisspeptin and testosterone concentrations were significantly higher in women with PCOS than controls: kisspeptin 4.873nmol/L versus 4.127nmol/L; testosterone 4.713nmol/L versus 3.415 nmol/L, p<0.05. Sequencing the GPR54 gene revealed 5 single nucleotide polymorphisms (SNPs), rs10407968, rs1250729403, rs350131, chr19:918686, and chr19:918735, with two novel SNPs (chr19:918686 and chr19:918735), while sequencing the Kiss1 gene revealed 2 SNPs, rs5780218 and rs4889. All identified SNPs showed no significant difference in frequency between patients and controls. GPR54 gene rs350131 polymorphism (G/T) was detected more frequently in our study population. The heterozygous allele (AG) of GPR54 gene novel polymorphism chr19:918686 showed a marginal association with serum kisspeptin levels (p=0.053). Genetic variations in GPR54 and Kiss1 genes are unlikely to be associated with PCOS among Sri Lankan women manifesting from adolescence. Meanwhile the heterozygous allele of chr19:918686 is probably associated with serum kisspeptin concentrations, which suggests a potential role in the aetiology of PCOS.

Dataset Information

The effect of intracerebroventricular administration of neuropeptide Y on reproductive axis function in the male Wistar rats: Involvement of hypothalamic KiSS1/GPR54 system.

Publications

The effect of intracerebroventricular administration of neuropeptide Y on reproductive axis function in the male Wistar rats: Involvement of hypothalamic KiSS1/GPR54 system.

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