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Jeremy T Smith, Antonia Roseweir, Michael Millar, Iain Clarke, Robert P Millar
Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin- releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in GH regulation by examining the effect of kisspeptin antagonists on growth hormone (GH) secretion in ewes under various physiological conditions...
March 16, 2018: Journal of Endocrinology
Muhammad Shahab, Margaret Lippincott, Yee-Ming Chan, Addie Davies, Paulina M Merino, Lacey Plummer, Veronica Mericq, Stephanie Seminara
Context: Hypothalamic kisspeptin signaling plays a critical role in the initiation and maintenance of reproductive function. Biallelic mutations in the coding sequence of KISS1R (GPR54) have been identified in patients with idiopathic hypogonadotropic hypogonadism (IHH), but it is unknown whether biallelic variants can also be associated with related reproductive disorders. Case description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was identified in a child who presented with microphallus and bilateral cryptorchidism...
February 14, 2018: Journal of Clinical Endocrinology and Metabolism
Hyo-Eun Son, Kyeong-Min Kim, Eun-Jung Kim, Won-Gu Jang
Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5)...
February 1, 2018: Scientific Reports
Tao Feng, Jiahua Bai, Xiaoling Xu, Yan Liu
Kisspeptin and its receptor, GPR54, are regarded as key regulators of and catalysts for male puberty onset, and also fundamental gatekeepers of spermatogenesis in mammals. Consequently, the loss function of kisspeptin or GPR54 leads to a symptom of hypogonadotropic hypogonadism (HH) in human and HH accompanied by lower gonadotrophic hormone levels, smaller testes, impaired spermatogenesis and abnormal sexual maturation in mice. Besides its well- recognized functions in hypothalamus before and during puberty, accumulating data strongly support kisspeptin production in tests, and participation in somatic and germ cell development and sperm functions as well...
January 28, 2018: Current Drug Metabolism
Wei Song, Kailin Li, Chao Sun, Jiang Xue
OBJECTIVE: We inferred how KISS-1/GPR54 system to involved in precocious puberty by observing hormones level during the process of precocious puberty in model and normal rats during sexual development and the estrus cycle. METHOD: Female rats were divided randomly into CPP and control groups; the former were injected with NMDA twice daily, and control groups were injected with saline. Blood and tissue samples were collected and measured during the stages of prepuberty, vaginal opening, estrus, proestrus and diestrus...
December 4, 2017: Neuro Endocrinology Letters
Zhu Zhu, Feng Huang, Feng Wang, Yonghong Zhang, Xiaozhen Zhao, Wei Wang
Varicoceles (VCs) are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis ( M. officinalis ) is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water-soluble polysaccharides extracted from M. officinalis (MOPs) on gonadotropin-release hormone (GnRH) secretion in a classic experimental left VC (ELV) rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg-1 to 100 mg kg-1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Jianhua Sun, Juxiong Liu, Bingxu Huang, Xingchi Kan, Guangxin Chen, Wei Wang, Shoupeng Fu
Kisspeptins (Kps) play a key role in the regulation of GnRH axis and as an anti-metastasis agent by binding with GPR54 . Recently, we observed that the expression of GPR54 was higher in the lactating mammary tissues of dairy cows with high-quality milk (0.81 ± 0.13 kg/day of milk protein yield; 1.07 ± 0.18 kg/day of milk fat yield) than in those with low-quality milk (0.51 ± 0.14 kg/day of milk protein yield; 0.67 ± 0.22 kg/day of milk fat yield). We hypothesized that Kp-10 might regulate the milk protein, β-casein (CSN2) synthesis via GPR54 and its downstream signaling...
December 5, 2017: International Journal of Molecular Sciences
Sareh Zeydabadi Nejad, Fahimeh Ramezani Tehrani, Azita Zadeh-Vakili
Context: Kisspeptin (KISS1), a recently discovered neuropeptide that acts upstream of gonadotropin-releasing hormone (GnRH) neurons, is critical for maturation and function of the reproductive axis. This review aimed at providing comprehensive and up-to-date information on Kisspeptin and its role in female reproduction. Evidence Acquisition: A literature review was performed using PubMed for all English language articles published between 1999 and 2016. Results: The kisspeptin system (KISS1/G protein-coupled receptor-54,GPR54) has recently been addressed as an essential gatekeeper of puberty onset and gonadotropin secretion...
July 2017: International Journal of Endocrinology and Metabolism
Y Liu, J H Bai, X L Xu, Z L Chen, L J Spicer, T Feng
Recent studies have shown that N-carbamylglutamate (NCG) and arginine (ARG) supplementation improves reproductive performance in livestock. The objectives of the present study were to evaluate the effects of NCG and ARG on GT1-7 cell gonadotrophin-releasing hormone (GnRH) secretion, gene expression and cell proliferation. GT1-7 cells were treated in vitro with different concentrations of NCG (0-1.0mM) or ARG (0-4.0mM) in serum-free medium for 12 or 24h. For GnRH secretion and cell proliferation, GT1-7 cells were more sensitive to NCG than ARG...
November 10, 2017: Reproduction, Fertility, and Development
Zonghao Yue, Miao Yu, Haifeng Zhao, Jun Wang, Xiaona Zhang, Hua Tian, Wei Wang, Shaoguo Ru
This study investigated the anti-estrogenic effects of chronic exposure to a new marine pollutant, semicarbazide (SMC; 1, 10, and 100μg/L), in female Paralichthys olivaceus, as well as the associated mechanism. After 130days of exposure, plasma 17β-estradiol and testosterone concentrations, and hepatic estrogen receptors, vitellogenin, and choriogenin mRNA levels decreased significantly in SMC-exposed groups. Moreover, down-regulation of genes in the hypothalamic-pituitary-gonadal axis, including gonadotropin-releasing hormone, gonadotropic hormones and their receptors, the steroidogenic acute regulatory protein, 17α-hydroxylase, 17β-hydroxysteroid dehydrogenase, and cytochrome P450 19A, was observed after SMC exposure...
October 31, 2017: Marine Pollution Bulletin
Mikoto Nakajo, Shinji Kanda, Tomomi Karigo, Akiko Takahashi, Yasuhisa Akazome, Yoshihisa Uenoyama, Makito Kobayashi, Yoshitaka Oka
Kisspeptin neuronal system, which consists of a neuropeptide kisspeptin and its receptor Gpr54, is considered in mammals a key factor of reproductive regulation, so called hypothalamic-pituitary-gonadal (HPG) axis. However, in non-mammalian vertebrates, especially in teleosts, existence of kisspeptin regulation on HPG axis is still controversial. Here, we applied multidisciplinary techniques to a teleost fish, medaka and examined possible kisspeptin regulation on HPG axis. First, we generated knockout medaka for kisspeptin-related genes and found that they show normal fertility, gonadal maturation, and expression of gonadotropins...
October 18, 2017: Endocrinology
Chenxi Li, Pin Li
BACKGROUND/AIMS: Enhance at puberty-1 (Eap1) is an intronless gene that regulates the onset of puberty through a network of hypothalamic genes. However, precise mechanistic events essential for Eap1-regulation of puberty have not been fully elucidated. Eap1 is thought to promote the initiation of puberty through regulation of the hypothalamic metastasis-suppressor KiSS1. We aim to investigate this hypothesis by genetically perturbing Eap1 through RNA interference in vivo. METHODS: We first engineered and optimized four sets of shRNAs that target rat Eap1 mRNA as well as one negative control shRNA...
2017: Cellular Physiology and Biochemistry
Tae-Hun Kim, Sung-Gook Cho
Kisspeptin is a protein encoded by the KISS1 gene, which has been reported to suppress the metastatic capabilities of various types of cancer cells, through the activation of its G‑protein coupled receptor GPR54. However, the molecular mechanisms underlying the involvement of kisspeptin‑mediated signaling in the inhibition of cancer cell migration and invasion have yet to be elucidated. The present in vitro cell proliferation, migration and invasion assays and in vivo experimental metastasis studies demonstrated that kisspeptin‑induced eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) activation suppressed the metastatic capabilities of several types of cancer cells...
November 2017: Molecular Medicine Reports
Rosanna Chianese, Vincenza Ciaramella, Silvia Fasano, Riccardo Pierantoni, Rosaria Meccariello
Kisspeptin (Kp) system has a recognized role in the control of gonadotropic axis, at multiple levels. Recently, a major focus of research has been to assess any direct activity of this system on testis physiology. Using the amphibian anuran, Pelophylax esculentus, as animal model, we demonstrate - for the first time in non-mammalian vertebrate - that testis expresses both Kiss-1 and Gpr54 proteins during the annual sexual cycle and that ex vivo 17B-estradiol (E2, 10(-6) M) increases both proteins over control group...
October 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
Bin-Qiao Wang, Yuan-Yuan Chen, Xiao-Xiao Lan, Zhi-Yang Zhou, Xin-Xin Xu, Xue-Qing Wu
Immune challenge in early life has been observed to influence the long-term reproductive dysfunction. On PNDs 3 and 5, female offsprings were administered with LPS (50μg/kg, i.p.) or saline. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 56-70 days. At 10 weeks of age, the ovaries were removed for immunostaining and RNA analysis. Neonatal exposure to LPS resulted in a significant delay puberty onset as well as destroyed expression of ovulation related genes...
December 2017: Reproductive Toxicology
Anuradha, Amitabh Krishna
Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis...
August 14, 2017: Molecular Reproduction and Development
Chrysoula Roufidou, Monika Schmitz, Ian Mayer, Marion Sebire, Ioanna Katsiadaki, Yi Ta Shao, Bertil Borg
Female three-spined sticklebacks are batch spawners laying eggs in a nest built by the male. We sampled female sticklebacks at different time points, when they were ready to spawn and 6, 24, 48 and 72 hours post-spawning (hps) with a male. Following spawning, almost all females (15 out of 19) had ovulated eggs again at Day 3 post-spawning (72hps). At sampling, plasma, brain and pituitaries were collected, and the ovary and liver were weighed. Testosterone (T) and estradiol (E2) were measured by radioimmunoassay...
August 2, 2017: General and Comparative Endocrinology
Willem Vannecke, Christophe Ampe, Marleen Van Troys, Massimiliano Beltramo, Annemieke Madder
Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of a furan-modified peptide ligand to its membrane-presented receptor with zero toxicity, high efficiency, and spatio-specificity. Furan-modified kisspeptin-10 is covalently coupled to its glycosylated membrane receptor, GPR54(KISS1R)...
July 17, 2017: ACS Chemical Biology
C H J Albers-Wolthers, J de Gier, M Walen, P J S van Kooten, C B Lambalk, P A J Leegwater, B A J Roelen, A C Schaefers-Okkens, V P M G Rutten, R P M Millar, H S Kooistra
Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the administration of KP10, they can serve as a good animal model for research concerning KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs p234, p271, p354, and p356 in vitro, by determining the intracellular Ca2+ response of CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides on basal plasma LH concentration and the KP10-induced LH response in female dogs...
2017: PloS One
Xingfa Han, Yuqin Zhou, Yu Zeng, Fenfen Sui, Yacheng Liu, Yao Tan, Xiaohan Cao, Xiaogang Du, Fengyan Meng, Xianyin Zeng
The objective was to compare effects of anti-GnRH immunization (immunocastration) versus surgical castration on hypothalamic-pituitary function in boars. Thirty-six boars were randomly divided into three groups (n = 12/group): control, surgically castrated, or immunized against GnRH at 10 wk of age (boostered 8 wk later). Compared to intact boars, immunocastration reduced (P < 0.05) serum concentrations of LH, FSH, testosterone and inhibin B and caused severe testicular atrophy, whereas surgical castration increased (P < 0...
July 15, 2017: Theriogenology
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