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Chrysanthi Fergani, Victor Navarro
Reproductive function is driven by the hormonal interplay between the gonads and brain-pituitary axis. Gonadotropin-releasing hormone (GnRH) is released in a pulsatile manner, which is critical for the attainment and maintenance of fertility, however, GnRH neurons lack the ability to directly respond to most regulatory factors, and a hierarchical upstream neuronal network governs its secretion. We and others proposed a model in which Kiss1 neurons in the arcuate nucleus (ARC), so called KNDy neurons, release kisspeptin (a potent GnRH secretagogue) in a pulsatile manner to drive GnRH pulses under the coordinated autosynaptic action of its cotransmitters, the tachykinin neurokinin B (NKB, stimulatory) and dynorphin (inhibitory)...
October 17, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
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
Marcio A Torsoni, Beatriz C Borges, Jessica L Cote, Susan J Allen, Erica Mahany, David Garcia-Galiano, Carol F Elias
A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal (HPG) axis is adaptive when energy reserves are diminished, allowing individual survival and energy accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor of the AMP/ATP ratio and ultimately of energy availability. Activation of AMPK suppresses ATP-consuming processes and stimulates ATP-producing pathways. The AMPK α2 catalytic subunit is expressed in multiple hypothalamic nuclei including those associated with reproductive control, i...
October 12, 2016: Endocrinology
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
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
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
F Espigares, A Rocha, A Gómez, M Carrillo, S Zanuy
The onset of puberty is characterized by activation of the brain-pituitary-gonad axis. However, the molecular and endocrine mechanism involved in the process of puberty and the influence of environmental conditions, such as photoperiod signalling, are not well understood in fish. In this study, 1-year-old male European sea bass (Dicentrarchus labrax) were exposed to photoperiod manipulation in combination with size-sorting. Two treatment groups, a puberty accelerating photoperiod (AP) group and a continuous light (LL) group, were studied from August to February...
September 15, 2016: General and Comparative Endocrinology
Michelle R Roberts, Lara E Sucheston-Campbell, Gary R Zirpoli, Michael Higgins, Jo L Freudenheim, Elisa V Bandera, Christine B Ambrosone, Song Yao
Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with pARTP  ≤ 0...
September 6, 2016: Molecular Carcinogenesis
L Chen, M Liu, J Ji, W Lin, F Shan, H Liu
To evaluate the diagnostic accuracy of peripheral blood kisspeptin (KISS1) mRNA and plasma cancer antigen 125 (CA125) protein of epithelial ovarian cancer (EOC) in previously pregnant patients, we prospectively enrolled 40 EOC patients as cases and 20 uterine fibroids patients with normal ovary as controls. Levels of peripheral blood KISS1 mRNA and plasma CA125 protein was respectively measured by RT-PCR and electrochemiluminescent method, respectively. Receiver operating characteristic curves with area under curve (AUC) were used to evaluate the diagnostic accuracy...
September 6, 2016: Neoplasma
Rosanna Chianese, Gilda Cobellis, Teresa Chioccarelli, Vincenza Ciaramella, Marina Migliaccio, Silvia Fasano, Riccardo Pieranton, Rosaria Meccariello
BACKGROUND: The control of male fertility requires accurate endocrine, paracrine and autocrine communications along the hypothalamus-pituitary-gonad (HPG) axis. In this respect, the possible interplay between upcoming/classical modulators of reproductive functions deserves attention in that may be a successful tool for the future exploitation of new potential therapeutic targets in the treatment of fertility disorders. METHODS: In this review we will discuss upcoming data concerning the role of kisspeptins, the products of the Kiss1 gene, and estrogens - classically considered as female hormones - as well as their possible interplay in testis...
September 2, 2016: Current Medicinal Chemistry
M V Alvarado, A Servili, G Molés, M M Gueguen, M Carrillo, O Kah, A Felip
Kisspeptins are well known as mediators of the coordinated communication between the brain-pituitary axis and the gonads in many vertebrates. To test the hypothesis that gonadal steroids regulate kiss1 and kiss2 mRNA expression in European sea bass (a teleost fish), we examined the brains of gonad-intact (Control) and castrated animals, as well as castrated males (GDX) and females (OVX) that received testosterone (T) and estradiol (E2) replacement, respectively, during recrudescence. In GDX males, low expression of kiss1 mRNA is observed by in situ hybridization in the caudal hypothalamus (CH) and the mediobasal hypothalamus (MBH), although hypothalamic changes in kiss1 mRNA levels were not statistically different among the groups as revealed by real-time PCR...
September 2, 2016: Journal of Experimental Biology
Naoki Nishizawa, Yoshihiro Takatsu, Satoshi Kumano, Atsushi Kiba, Junko Ban, Shunichirou Tsutsumi, Hisanori Matsui, Shin-Ichi Matsumoto, Masashi Yamaguchi, Yukihiro Ikeda, Masami Kusaka, Tetsuya Ohtaki, Fumio Itoh, Taiji Asami
Metastin/kisspeptin is an endogenous ligand of KISS1 Receptor (KISS1R). Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of gonadotropin-releasing hormone (GnRH), and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. Our optimization studies of metastin derivatives led to the discovery of 1 (Ac-d-Tyr-d-Trp-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2, TAK-683), which suppressed plasma testosterone in rats at lower doses than those of leuprolide...
October 13, 2016: Journal of Medicinal Chemistry
Shannon B Z Stephens, Navdeep Chahal, Nagambika Munaganuru, Ruby A Parra, Alexander S Kauffman
The neuropeptide kisspeptin, encoded by Kiss1, regulates reproduction by stimulating GnRH secretion. Neurons synthesizing kisspeptin are predominantly located in the hypothalamic anteroventral periventricular (AVPV) and arcuate nuclei, but smaller kisspeptin neuronal populations also reside in extrahypothalamic brain regions, such as the medial amygdala (MeA). In adult rodents, estradiol (E2) increases Kiss1 expression in the MeA, as in the AVPV. However, unlike AVPV and arcuate nuclei kisspeptin neurons, little else is currently known about the development, regulation, and function of MeA Kiss1 neurons...
October 2016: Endocrinology
Christelle Doebelin, Isabelle Bertin, Séverine Schneider, Martine Schmitt, Jean-Jacques Bourguignon, Caroline Ancel, Valerie Simonneaux, Frédéric Simonin, Frédéric Bihel
A series of dipeptides were designed as potential agonists of the human KiSS1-derived peptide receptor (hGPR54). While the sequence Arg-Trp-NH2 was the most efficient in terms of affinity, we established a convergent synthetic strategy to optimize the N terminus. Using two successive Sonogashira cross-coupling reactions on a solid-supported peptide, we were able to introduce various alkynes at the N terminus to afford compounds with sub-micromolar affinities for hGPR54. However, functional assays indicated the benzoylated dipeptide Bz-Arg-Trp-NH2 as the most promising compound in terms of agonistic properties...
October 6, 2016: ChemMedChem
Irma Airoldi, Claudia Cocco, Carlo Sorrentino, Domenico Angelucci, Serena Di Meo, Lamberto Manzoli, Silvia Esposito, Domenico Ribatti, Maria Bertolotto, Laura Iezzi, Clara Natoli, Emma Di Carlo
The inflammatory tissue microenvironment which promotes the development of breast cancer (BRCA) is not fully understood. Here we report a role for elevated IL-30 in supporting the BRCA cell viability and invasive migration. IL-30 was absent in normal mammary ducts, ductules and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, its IL-30 was expressed frequently in BRCA specimens where it was associated with triple-negative and HER2+ molecular subtypes...
August 22, 2016: Cancer Research
Jian Qiu, Casey C Nestor, Chunguang Zhang, Stephanie L Padilla, Richard D Palmiter, Martin J Kelly, Oline K Rønnekleiv
Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice...
2016: ELife
Haijie Ma, Xuepeng Sun, Mingshuang Wang, Yunpeng Gai, Kuang-Ren Chung, Hongye Li
The postharvest pathogen Penicillium digitatum causes green mold decay on citrus fruit, resulting in severe economic losses. To explore possible factors involved in fungal pathogenesis, phenotypic characterization of the budding yeast Fus3/Kiss1 mitogen-activated protein (MAP) kinase homolog was carried out. The P. digitatum MAP kinase B coding gene, designated PdMpkB, was functionally inactivated via homologous recombination. The fungal strain (∆PdMpkB) carrying a PdMpkBdeletion demonstrated altered gene expression profiles, reduced growth and conidiogenesis, elevated resistance to osmotic stress, and failed to induce green mold decay on citrus fruit...
November 7, 2016: International Journal of Food Microbiology
Rong Yang, Yi-Mei Wang, Li Zhang, Zeng-Ming Zhao, Jun Zhao, Shuang-Qing Peng
Sporadic epidemics and several researches in rodents indicated that zearalenone (ZEA) and its metabolites, the prevailing oestrogenic mycotoxins in foodstuffs, were a triggering factor for true precocious puberty development in girls. Nevertheless, the neuroendocrine mechanism through which ZEA mycoestrogens advance puberty onset is not fully understood. To elucidate this issue, hypothalamic kisspeptin-G-protein coupled receptor-54 (GPR54) signaling pathway that regulates the onset of puberty was focused on in the present study...
December 5, 2016: Molecular and Cellular Endocrinology
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