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Virginia Mela, Sara Jimenez, Alejandra Freire-Regatillo, Vicente Barrios, Eva-María Marco, Ana-Belén Lopez-Rodriguez, Jesús Argente, María-Paz Viveros, Julie A Chowen
The neonatal leptin surge, occurring from postnatal day (PND) 5 to 13 and peaking at PND9 in rodents, is important for the development of neuroendocrine circuits involved in metabolic control and reproductive function. We previously demonstrated that treatment with a leptin antagonist from PND 5 to 9, coincident with peak leptin levels in the neonatal surge, modified trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus of peri-pubertal rats. The kisspeptin system and metabolic neuropeptide and hormone levels were also modified...
October 14, 2016: Peptides
Erica Sarchielli, Paolo Comeglio, Roberta Squecco, Lara Ballerini, Tommaso Mello, Giulia Guarnieri, Eglantina Idrizaj, Benedetta Mazzanti, Linda Vignozzi, Pasquale Gallina, Mario Maggi, Gabriella B Vannelli, Annamaria Morelli
CONTEXT: Previous studies have suggested that inflammatory pathways may impair central regulatory networks involving gonadotropin-releasing hormone (GnRH) neuron activity. Studies in humans are strongly hampered by the lack of human GnRH neuron cell lines. OBJECTIVE: To establish an in vitro model of GnRH neurons of human origin and analyze the effects of proinflammatory cytokines on their biological properties. Design, samples and treatments: The primary human fetal hypothalamic (hfHypo) cell cultures were isolated from brain of three 12 week-old fetuses...
October 13, 2016: Journal of Clinical Endocrinology and Metabolism
Chrysanthi Fergani, Leanne Mazzella, Lique M Coolen, Richard B McCosh, Steven L Hardy, Nora Newcomb, Pasha Grachev, Michael N Lehman, Robert L Goodman
There is now general agreement that neurokinin B (NKB) acts via NK3R to stimulate secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) in several species, including rats, mice, sheep, and humans. However the roles of two other tachykinins, substance P (SP) and neurokinin A (NKA), which act primarily via NK1R and NK2R respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus...
October 5, 2016: Endocrinology
Tobias Hofmann, Ulf Elbelt, Verena Haas, Anne Ahnis, Burghard F Klapp, Matthias Rose, Andreas Stengel
While physical hyperactivity represents a frequent symptom of anorexia nervosa and may have a deleterious impact on the course of the disease, the underlying mechanisms are poorly understood. Since several food intake-regulatory hormones affect physical activity, the aim of the study was to investigate the association of physical activity with novel candidate hormones (kisspeptin, ghrelin, oxyntomodulin, orexin-A, FGF-21, R-spondin-1) possibly involved in patients with anorexia nervosa. Associations with psychometric parameters and body composition were also assessed...
September 28, 2016: Appetite
Maria Manfredi-Lozano, Juan Roa, Francisco Ruiz-Pino, Richard Piet, David Garcia-Galiano, Rafael Pineda, Aurora Zamora, Silvia Leon, Miguel A Sanchez-Garrido, Antonio Romero-Ruiz, Carlos Dieguez, Maria Jesus Vazquez, Allan E Herbison, Leonor Pinilla, Manuel Tena-Sempere
OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction...
October 2016: Molecular Metabolism
Joanna Helena Sliwowska, Wendy L Comeau, Tamara S Bodnar, Linda Ellis, Joanne Weinberg
BACKGROUND: Reproductive maturation is initiated with the onset of puberty, which activates the hypothalamic-pituitary-gonadal axis and coincidences with increased expression of the hormone kisspeptin within the hypothalamus. Maturational events are sensitive to environmental factors, including alcohol, which is known to delay reproductive development. We hypothesized that, similar to alcohol's adverse effects during reproductive maturation, prenatal alcohol exposure (PAE) would alter pubertal markers, sex hormone profiles, and kisspeptin expression in the hypothalamus...
September 30, 2016: Alcoholism, Clinical and Experimental Research
Shubo Jin, Dajiang Sun, Qingkai Xi, Xiaoli Dong, Dan Song, Hongtuo Fu, Ying Zhang
Kisspeptin plays an important role in the reproduction and onset of puberty in vertebrates through stimulation of gonadotropin-releasing hormone (GnRH). However, the mechanisms whereby kisspeptin-related genes regulate sexual differentiation in teleosts are poorly understood. We aimed to study the relationship between the hypothalamus-pituitary-gonad (HPG) axis and sexual differentiation in relation to kisspeptin in the sturgeon Acipenser schrenckii. We performed comparative transcriptomic analysis of the brains of sturgeons treated with KISS1-10 during the gonadal sex-differentiation-sensitive period (170-210days post-hatching (dph)) using an Illumina sequencing platform...
September 26, 2016: Gene
Mohd Ashraf Rather, Irfan Ahmad Bhat, Pravesh Kumar Rathor, P Gireesh-Babu, Aparna Chaudhari, Sundaray Jeetendra Kumar, Rupam Sharma
We report the characterization of kisspeptin gene which is considered to be essential for successful animal reproduction. The full-length cDNA sequence of kiss2 was 583 bp, consisted of 11 bp 5'-UTR (untranslated region) and 194 bp 3'-UTR, respectively. Open reading frame of 378 bp encoding a putative protein of 125 amino acids. The Catla catla kiss2 protein was having a molecular weight of 14.51 kDa and isoelectric point (pI) of 8.46. There were four serine (Ser), four threonine (Thr) and two tyrosine (Tyr) phosphorylation sites and no N-glycosylation sites on the predicted protein...
September 29, 2016: Journal of Biomolecular Structure & Dynamics
Haruhiko Kanasaki, Aki Oride, Tomomi Hara, Tselmeg Mijiddorj, Unurjargal Sukhbaatar, Satoru Kyo
Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-both gonadotropins-from pituitary gonadotrophs, it has recently become clear that hypothalamic GnRH is under the control of hypothalamic kisspeptin...
2016: International Journal of Molecular Sciences
Charles E Roselli, Rebecka Amodei, Kyle Gribbin, Keely Corder, Fred Stormshak, Charles T Estill
Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess testosterone exposure. The objective of this study was to determine the effect of exogenous exposure to testosterone on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to 58 of gestation acutely decreased (P<0...
September 27, 2016: Endocrinology
Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Takeshi Iwasa, Munkhsaikhan Munkhzaya, Rie Yanagihara, Takako Tokui, Kiyohito Yano, Yiliyasi Mayila, Takeshi Kato, Akira Kuwahara, Sumika Matsui, Minoru Irahara
Hypersecretion of luteinizing hormone (LH) is a common endocrinological finding of polycystic ovary syndrome (PCOS). This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs of 3-week-old female Wistar rats...
September 24, 2016: Endocrine Journal
Shel Hwa Yeo, Victoria Kyle, Paul G Morris, Sophie Jackman, Lydia Sinnett-Smith, Maria Schacker, Chen Chen, William H Colledge
Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurons are found in two locations in the rodent hypothalamus; one in the arcuate (ARC) and another in the RP3V region which includes the anteroventral periventricular (AVPV) nucleus. Detailed mapping of the fibre distribution of Kiss1 neurons will help in understanding the action of these neurons in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region has been disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter...
September 24, 2016: Journal of Neuroendocrinology
Amir Babiker, Adnan Al Shaikh
Kisspeptin (previously known as metastin) is a protein encoded by the KISS-1 gene in humans. Kisspeptin producing neurons seem to bridge the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone secretion. Since 2003, there are many studies on the facets of neuroendocrine networks that control puberty and fertility. These have explored the role of Kisspeptins in puberty and fertility using animal models. Kisspeptins are universally recognized as essential activators of the gonadotropic axis and they play an essential role in the metabolic regulation of fertility...
2016: Sudan J Paediatr
Kristen P Tolson, Christian Garcia, Iris Delgado, Nuha Marooki, Alexander S Kauffman
Kisspeptin regulates reproduction via signaling through the receptor, Kiss1r, in GnRH neurons. However, both kisspeptin and Kiss1r are produced in several peripheral tissues, and recent studies have highlighted a role for kisspeptin signaling in metabolism and glucose homeostasis. We recently reported that Kiss1r KO mice display a sexually-dimorphic metabolic phenotype, with KO females displaying obesity, impaired metabolism, and glucose intolerance at 4-5 months of age. However, it remains unclear when this metabolic phenotype first emerges in development, or which aspects of the pleiotropic phenotype underlie the metabolic defects and which are secondary to the obesity...
September 20, 2016: Endocrinology
Hirofumi Ohga, Daisuke Hirata, Kojiro Matsumori, Hajime Kitano, Naoki Nagano, Akihiko Yamaguchi, Michiya Matsuyama
Leptin directly regulates kisspeptin neurons in the hypothalamus and gonadotropin secretion from the pituitary, making it a central player in the onset of mammalian puberty. Recently, we identified two leptin genes (lepa and lepb) and a single leptin receptor (lepr) in the marine perciform fish chub mackerel; however, the expression of these genes did not correlate with the expression of important reproductive genes or ovarian stage during female puberty. Here, we expand upon these initial observations by evaluating the expression of lepa, lepb, and lepr during pubertal transition and under differential feeding conditions in the male chub mackerel...
September 15, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Karolina Skorupskaite, Jyothis T George, Johannes D Veldhuis, Robert P Millar, Richard A Anderson
CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with NK3R antagonist followed by transdermal estradiol to induce LH secretion 48hr later, with kisspeptin-10 or vehicle infusion during estrogen administration in a two-way cross-over study...
September 16, 2016: Journal of Clinical Endocrinology and Metabolism
Manish Putteeraj, Tomoko Soga, Takayoshi Ubuka, Ishwar S Parhar
Reproduction is associated with the circadian system, primarily as a result of the connectivity between the biological clock in the suprachiasmatic nucleus (SCN) and reproduction-regulating brain regions, such as preoptic area (POA), anteroventral periventricular nucleus (AVPV), and arcuate nucleus (ARC). Networking of the central pacemaker to these hypothalamic brain regions is partly represented by close fiber appositions to specialized neurons, such as kisspeptin and gonadotropin-releasing hormone (GnRH) neurons; accounting for rhythmic release of gonadotropins and sex steroids...
2016: Frontiers in Endocrinology
Hasan Öztin, Eylem Çağıltay, Sinan Çağlayan, Mustafa Kaplan, Yaşam Kemal Akpak, Nilay Karaca, Mesut Tığlıoğlu
Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH)...
September 10, 2016: Gynecological Endocrinology
Julie-Ann P De Bond, Kristen P Tolson, Chanond Nasamran, Alexander S Kauffman, Jeremy T Smith
Kisspeptin controls reproduction by stimulating GnRH neurons via its receptor Kiss1r. Kiss1r is also expressed other brain areas and in peripheral tissues, suggesting additional non-reproductive roles. We recently determined that Kiss1r knockout (KO) mice develop an obese and diabetic phenotype. Here, we investigated whether Kiss1r KOs develop this metabolic phenotype due to alterations in the expression of metabolic genes involved in the appetite regulating system of the hypothalamus, including neuropeptide Y (Npy) and pro-opiomelanocortin (Pomc), as well as leptin receptor (Lepr), ghrelin receptor (Ghsr), and melanocortin receptor 3 and 4 (Mc3r, Mc4r)...
September 7, 2016: Journal of Neuroendocrinology
Xiaoxiao Gao, Kaifa Zhang, Min Song, Xiumei Li, Lei Luo, Yuan Tian, Yunhai Zhang, Yunsheng Li, Xiaorong Zhang, Yinghui Ling, Fugui Fang, Ya Liu
Nesfatin-1 is an important molecule in the regulation of reproduction. However, its role in the reproductive axis in male animals remains to be understood. Here, we found that nesfatin-1 was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN), periventricular nucleus (PeN), and lateral hypothalamic area (LHA) of the hypothalamus; adenohypophysis and Leydig cells in male rats. Moreover, the concentrations of serum nesfatin-1 and its mRNA in hypothalamo-pituitary-gonadal axis (HPGA) vary with the age of the male rat...
2016: Scientific Reports
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