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Psychiatria Polska Feb 2024The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents...
OBJECTIVES
The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents suffering from bipolar disorder, and by this their predictive efficiency in this disorder.
METHODS
The study covered 75 individuals with a mean age of 15.26 years (95% CI: 14.86-15.67), of which the study group comprised of 57 individuals diagnosed with bipolar affective disorder and the control group - 18 individuals with no psychiatric diagnosis and no pharmacological treatment. Phoenixin, spexin and kisspeptin levels were determined in the peripheral venous blood serum. Neuropeptide concentrations were measured with the enzyme-linked immunosorbent assay (ELISA).
RESULTS
The mean phoenixin concentration in the studied group equalled 1.57 ng/ml (95% CI: 1.35-1.79), while in the control group - 2.69 ng/ml (95% CI: 2.38-3; U Mann-Whitney test p-value < 0.05). For spexin, these results were 639.65 pg/ml (95% CI: 558.86-720.44) in the studied group, and 354.28 pg/ml (95% CI: 310.33-398.22; U Mann-Whitney test p-value < 0.05) in the control group. The observed differences were statistically significant. The mean concentration of kisspeptin levels in the studied group was 126.02 pg/ml (95% CI: 39.82-212.23; median: 59.85), while in the control group - 54.83 pg/ml (95% CI: 39.23-70.43; median: 51.3; U Mann-Whitney test p-value = 0.29), and the observed difference was not statistically significant.
CONCLUSIONS
The occurrence of bipolar disorder symptoms is statistically significantly linked with a decreased phoenixin concentration and to a small degree - with an increased spexin concentration in blood serum of patients. However, it is not linked with the kisspeptin concentration.
Topics: Humans; Bipolar Disorder; Kisspeptins; Female; Male; Adolescent; Peptide Hormones; Neuropeptides; Biomarkers; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay
PubMed: 36989336
DOI: 10.12740/PP/OnlineFirst/155178 -
Angewandte Chemie (International Ed. in... May 2023The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited...
The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging.
Topics: Mice; Animals; Humans; Kisspeptins; Peptides; Islets of Langerhans; Receptors, G-Protein-Coupled; Optical Imaging; Amino Acids
PubMed: 36917014
DOI: 10.1002/anie.202302688 -
Iranian Journal of Medical Sciences Mar 2023Sperm cryopreservation reduces sperm quality. Kisspeptin (KP) has beneficial effects on sperm functions. This study compares the effect of KP and Glutathione (GSH) on...
BACKGROUND
Sperm cryopreservation reduces sperm quality. Kisspeptin (KP) has beneficial effects on sperm functions. This study compares the effect of KP and Glutathione (GSH) on mitigating the detrimental effects of the freeze-thaw cycle on sperm.
METHODS
An experimental study was conducted in Birjand (Iran) during 2018-2020. Thirty normal swim-up semen samples were treated with Ham's F10 medium (negative control), 1 mM GSH (positive control), or KP (10 µM) for 30 min before freezing. The motility, acrosome reaction, capacitation, and DNA quality of the frozen-thawed sperms were assessed according to the WHO guidelines. Statistical analysis was performed using paired test, one-way analysis of variance, and least significant difference.
RESULTS
Pre-incubation with KP significantly increased the percentage of sperm motility (34.00±6.7, P=0.003) compared to the control (20.44±7.4) and GSH-treated (31.25±12.2) aliquots. The frequency of non-capacitated spermatozoa was significantly higher in the KP-treated group (98.73%) than in the control (96.46%) and GSH-treated (96.49%) aliquots (P<0.001). The percentage of acrosome-intact spermatozoa in the KP-treated group (77.44%) was significantly higher than the control (74.3%) and GSH-treated (74.54%) groups (P<0.001). The sperm frequency with normal histone in the KP-treated group (51.86%) and with normal protamine (65.39%) was significantly higher than the controls (P=0.001 and P=0.002, respectively). The percentage of TUNEL-positive sperm was significantly lower in the KP-treated group (9.09±2.71) than both GSH-treated (11.22±2.73) and control (11.31±2.2) groups (both P=0.002).
CONCLUSION
Pre-incubation with KP protects sperm motility and DNA integrity from the detrimental effect of the freeze-thaw cycle. KP is suitable as a pre-treatment to control sperm quality during freezing-thawing.
Topics: Male; Humans; Freezing; Kisspeptins; Semen; Sperm Motility; Semen Preservation; Spermatozoa; Cryopreservation; Glutathione
PubMed: 36895454
DOI: 10.30476/IJMS.2022.92300.2354 -
Endocrine Journal Apr 2023After the discovery of GnRH, GnRH neurons have been considered to represent the final common pathway for the neural control of reproduction. There is now compelling data...
After the discovery of GnRH, GnRH neurons have been considered to represent the final common pathway for the neural control of reproduction. There is now compelling data in mammals that two populations of kisspeptin neurons constitute two different systems to control the episodic and surge release of GnRH/LH for the control of different aspects of reproduction, follicular development and ovulation. However, accumulating evidence indicates that kisspeptin neurons in non-mammalian species do not serve as a regulator of reproduction, and the non-mammalian species are believed to show only surge release of GnRH to trigger ovulation. Therefore, the GnRH neurons in non-mammalian species may offer simpler models for the study of their functions in neuroendocrine regulation of reproduction, especially ovulation. Our research group has taken advantage of many unique technical advantages of small fish brain for the study of anatomy and physiology of GnRH neurons, which underlie regular ovulatory cycles during the breeding season. Here, recent advances in multidisciplinary study of GnRH neurons are reviewed, with a focus on studies using small teleost fish models.
Topics: Female; Animals; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Kisspeptins; Reproduction; Neurons; Brain; Mammals
PubMed: 36889690
DOI: 10.1507/endocrj.EJ22-0669 -
Frontiers in Endocrinology 2023Reproduction is regulated through the hypothalamic-pituitary-gonadal (HPG) axis, largely the action of kisspeptin neurons in the hypothalamus. Importantly, neurons...
Reproduction is regulated through the hypothalamic-pituitary-gonadal (HPG) axis, largely the action of kisspeptin neurons in the hypothalamus. Importantly, neurons have been identified in other brain regions, including the medial amygdala (MeA). Though the MeA is implicated in regulating aspects of both reproductive physiology and behavior, as well as non-reproductive processes, the functional roles of MeA neurons are largely unknown. Additionally, besides their stimulation by estrogen, little is known about how MeA neurons are regulated. Using a RiboTag mouse model in conjunction with RNA-seq, we examined the molecular profile of MeA neurons to identify transcripts that are co-expressed in MeA neurons of female mice and whether these transcripts are modulated by estradiol (E) treatment. RNA-seq identified >13,800 gene transcripts co-expressed in female MeA neurons, including genes for neuropeptides and receptors implicated in reproduction, metabolism, and other neuroendocrine functions. Of the >13,800 genes co-expressed in MeA neurons, only 45 genes demonstrated significantly different expression levels due to E treatment. Gene transcripts such as , , and increased in response to E treatment, while fewer transcripts, such as and , were downregulated by E. Dual RNAscope and immunohistochemistry was performed to validate co-expression of MeA with and . These results are the first to establish a profile of genes actively expressed by MeA neurons, including a subset of genes regulated by E, which provides a useful foundation for future investigations into the regulation and function of MeA neurons.
Topics: Mice; Female; Animals; Kisspeptins; Estradiol; Phenotype; Amygdala; Neurons
PubMed: 36843592
DOI: 10.3389/fendo.2023.1093592 -
Animals : An Open Access Journal From... Feb 2023Kisspeptins are neuropeptides encoded by the gene, and little is known about them outside the vertebrate lineage. Two kisspeptin-type neuropeptides (KPs) have been...
Kisspeptins are neuropeptides encoded by the gene, and little is known about them outside the vertebrate lineage. Two kisspeptin-type neuropeptides (KPs) have been discovered in (AjK1 and AjK2), an edible sea cucumber, and have been linked to reproductive and metabolic regulation. In this study, we evaluated how KPs affected locomotor behavior in one control group and two treatment groups (AjK1 and AjK2). We discovered that AjK1 had a significant dose effect, primarily by shortening the stride length and duration of movement to reduce the sea cucumber movement distance, whereas AjK2 had little inhibitory effect at the same dose. The levels of phosphatidylethanolamine (PE), phosphatidylcholine (PC), uridine, glycine, and L-serine in the longitudinal muscle of treated with AjK1 differed significantly from those of the control, which may explain the observed changes in locomotor behavior. Treatment with AjK2 induced changes in aspartate levels. Our results imply that AjK1 is more likely than AjK2 to have a role in the regulation of locomotion.
PubMed: 36830492
DOI: 10.3390/ani13040705 -
Gynecological Endocrinology : the... Dec 2023To explore the association of , , vitamin D receptor () estrogen receptor α () gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone...
OBJECTIVES
To explore the association of , , vitamin D receptor () estrogen receptor α () gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone levels in EFP cases, in Chinese girls.
METHODS
The analysis was based on the data of 141 girls with EFP and 152 girls without EFP. Clinical features were documented, and all SNP genotyping was conducted using SNaPshot method. Statistical analysis was performed to assess the association of the SNPs with EFP risk, and with hormone levels in EFP cases.
RESULTS
There was a significant association between rs7759938-C polymorphism in the gene and the risk for EFP in the recessive (TT + CT vs. CC) model ( = 0.040). Remarkably, rs5780218-delA polymorphism in the gene and rs2234693-C polymorphism in the gene were significantly associated with peak LH (luteinizing hormone) levels ( = 0.008, 0.045) and peak LH/FSH (follicle-stimulating hormone) ratio ( 0.007, 0.006). Additionally, on 7 of the 8 variant loci the alleles associated with increased levels of both peak LH levels and peak LH/FSH ratio in EFP cases were also associated with increased CPP risk.
CONCLUSIONS
Our findings indicate that rs7759938-C polymorphism in the gene might have a protective effect on EFP susceptibility. The most striking findings of this study is that, rs5780218-delA polymorphism in the gene and rs2234693-C polymorphism in the gene influenced levels of GnRH-stimulated peak LH and LH/FSH ratio, and in general CPP risk genes might also contributes to the abnormality of hormonal levels in EFP.
Topics: Female; Humans; East Asian People; Estrogen Receptor alpha; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Kisspeptins; Luteinizing Hormone; Polymorphism, Single Nucleotide; Puberty; Puberty, Precocious; Receptors, Calcitriol; RNA-Binding Proteins
PubMed: 36828304
DOI: 10.1080/09513590.2023.2181653 -
The Journal of Neuroscience : the... Mar 2023Ovulation disorders are a serious problem for humans and livestock. In female rodents, kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) are...
Ovulation disorders are a serious problem for humans and livestock. In female rodents, kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) are responsible for generating a luteinizing hormone (LH) surge and consequent ovulation. Here, we report that adenosine 5-triphosphate (ATP), a purinergic receptor ligand, is a possible neurotransmitter that stimulates AVPV kisspeptin neurons to induce an LH surge and consequent ovulation in rodents. Administration of an ATP receptor antagonist (PPADS) into the AVPV blocked the LH surge in ovariectomized (OVX) rats treated with a proestrous level of estrogen (OVX + high E2) and significantly reduced the ovulation rate in proestrous ovary-intact rats. AVPV ATP administration induced a surge-like LH increase in OVX + high E2 rats in the morning. Importantly, AVPV ATP administration could not induce the LH increase in KO rats. Furthermore, ATP significantly increased intracellular Ca levels in immortalized kisspeptin neuronal cell line, and coadministration of PPADS blocked the ATP-induced Ca increase. Histologic analysis revealed that the proestrous level of estrogen significantly increased the number of P2X2 receptor (an ATP receptor)-immunopositive AVPV kisspeptin neurons visualized by tdTomato in -tdTomato rats. The proestrous level of estrogen significantly increased varicosity-like vesicular nucleotide transporter (a purinergic marker)-immunopositive fibers projecting to the vicinity of AVPV kisspeptin neurons. Furthermore, we found that some hindbrain vesicular nucleotide transporter-positive neurons projected to the AVPV and expressed estrogen receptor α, and the neurons were activated by the high E2 treatment. These results suggest that hindbrain ATP-purinergic signaling triggers ovulation via activation of AVPV kisspeptin neurons. Ovulation disorders, which cause infertility and low pregnancy rates, are a serious problem for humans and livestock. The present study provides evidence that adenosine 5-triphosphate, acting as a neurotransmitter in the brain, stimulates kisspeptin neurons in the anteroventral periventricular nucleus, known as the gonadotropin-releasing hormone surge generator, via purinergic receptors to induce the gonadotropin-releasing hormone/luteinizing hormone surge and ovulation in rats. In addition, histologic analyses indicate that adenosine 5-triphosphate is likely to be originated from the purinergic neurons in the A1 and A2 of the hindbrain. These findings may contribute to new therapeutic controls for hypothalamic ovulation disorders in humans and livestock.
Topics: Humans; Rats; Female; Animals; Kisspeptins; Estradiol; Luteinizing Hormone; Hypothalamus, Anterior; Gonadotropin-Releasing Hormone; Estrogens; Neurons; Ovulation; Rhombencephalon; Adenosine Triphosphate; Nucleotides; Receptors, Purinergic P2; Adenosine
PubMed: 36813577
DOI: 10.1523/JNEUROSCI.1496-22.2023 -
Journal of Toxicology and Environmental... Mar 2023The widespread use of 17α-ethinylestradiol (EE2), and other estrogenic endocrine disruptors, results in a continuous release of estrogenic compounds into aquatic...
The widespread use of 17α-ethinylestradiol (EE2), and other estrogenic endocrine disruptors, results in a continuous release of estrogenic compounds into aquatic environments. Xenoestrogens may interfere with the neuroendocrine system of aquatic organisms and may produce various adverse effects. The aim of the present study was to expose European sea bass larvae () to EE2 (0.5 and 50 nM) for 8 d and determine the expression levels of brain aromatase (), gonadotropin-releasing hormones (), kisspeptins (, ) and estrogen receptors (). Growth and behavior of larvae as evidenced by locomotor activity and anxiety-like behaviors were measured 8 d after EE2 treatment and a depuration period of 20 d. Exposure to 0.5 nM EE2 induced a significant increase in expression levels, while upregulation of , , and expression was noted after 8 d at 50 nM EE2. Standard length at the end of the exposure phase was significantly lower in larvae exposed to 50 nM EE2 than in control; however, this effect was no longer observed after the depuration phase. The upregulation of , , and expression levels was found in conjunction with elevation in locomotor activity and anxiety-like behaviors in larvae. Behavioral alterations were still detected at the end of the depuration phase. Evidence indicates that the long-lasting effects of EE2 on behavior might impact normal development and subsequent fitness of exposed fish.
Topics: Animals; Bass; Kisspeptins; Ethinyl Estradiol; Larva; Neurosecretory Systems
PubMed: 36803253
DOI: 10.1080/15287394.2023.2177781 -
Peptides May 2023Gonadal steroid feedback regulates the brain's patterned secretion of gonadotropin-releasing hormone (GnRH). Negative feedback, which occurs in males and during the... (Review)
Review
Gonadal steroid feedback regulates the brain's patterned secretion of gonadotropin-releasing hormone (GnRH). Negative feedback, which occurs in males and during the majority of the female cycle, modulates the amplitude and frequency of GnRH pulses. Positive feedback occurs in females when high estradiol induces a surge pattern of GnRH release. These two forms of feedback and their corresponding patterns of GnRH secretion are thought to be mediated by kisspeptin-expressing neurons in two hypothalamic areas: the arcuate nucleus and the anteroventral periventricular area. In this review, we present evidence for this theory and remaining questions to be addressed.
Topics: Male; Female; Humans; Estradiol; Kisspeptins; Feedback; Neurons; Gonadotropin-Releasing Hormone
PubMed: 36740189
DOI: 10.1016/j.peptides.2023.170963