scholarly journals Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice

2020 ◽  
Vol 21 (17) ◽  
pp. 5991
Author(s):  
Santosh Rijal ◽  
Dong Hyu Cho ◽  
Seon-Ah Park ◽  
Seon Hui Jang ◽  
István M. Ábrahám ◽  
...  

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.

2020 ◽  
Vol 21 (2) ◽  
pp. 529 ◽  
Author(s):  
Klaudia Barabás ◽  
Edina Szabó-Meleg ◽  
István M. Ábrahám

Inflammation has a well-known suppressive effect on fertility. The function of gonadotropin-releasing hormone (GnRH) neurons, the central regulator of fertility is substantially altered during inflammation in females. In our review we discuss the latest results on how the function of GnRH neurons is modified by inflammation in females. We first address the various effects of inflammation on GnRH neurons and their functional consequences. Second, we survey the possible mechanisms underlying the inflammation-induced actions on GnRH neurons. The role of several factors will be discerned in transmitting inflammatory signals to the GnRH neurons: cytokines, kisspeptin, RFamide-related peptides, estradiol and the anti-inflammatory cholinergic pathway. Since aging and obesity are both characterized by reproductive decline our review also focuses on the mechanisms and pathophysiological consequences of the impact of inflammation on GnRH neurons in aging and obesity.


2020 ◽  
Vol 7 (8) ◽  
pp. 201040
Author(s):  
Jonathon Penix ◽  
R. Anthony DeFazio ◽  
Eden A. Dulka ◽  
Santiago Schnell ◽  
Suzanne M. Moenter

Gonadotropin-releasing hormone (GnRH) neurons form the final pathway for the central neuronal control of fertility. GnRH is released in pulses that vary in frequency in females, helping drive hormonal changes of the reproductive cycle. In the common fertility disorder polycystic ovary syndrome (PCOS), persistent high-frequency hormone release is associated with disrupted cycles. We investigated long- and short-term action potential patterns of GnRH neurons in brain slices before and after puberty in female control and prenatally androgenized (PNA) mice, which mimic aspects of PCOS. A Monte Carlo (MC) approach was used to randomize action potential interval order. Dataset distributions were analysed to assess (i) if organization persists in GnRH neuron activity in vitro , and (ii) to determine if any organization changes with development and/or PNA treatment. GnRH neurons in adult control, but not PNA, mice produce long-term patterns different from MC distributions. Short-term patterns differ from MC distributions before puberty but become absorbed into the distributions with maturation, and the distributions narrow. These maturational changes are blunted by PNA treatment. Firing patterns of GnRH neurons in brain slices thus maintain organization dictated at least in part by the biologic status of the source and are disrupted in models of disease.


Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 463-468 ◽  
Author(s):  
Elizabeth P. Bless ◽  
Heather J. Walker ◽  
Kwok W. Yu ◽  
J. Gabriel Knoll ◽  
Suzanne M. Moenter ◽  
...  

Neurons that synthesize GnRH control the reproductive axis and migrate over long distances and through different environments during development. Prior studies provided strong clues for the types of molecules encountered and movements expected along the migratory route. However, our studies provide the first real-time views of the behavior of GnRH neurons in the context of an in vitro preparation that maintains conditions comparable to those in vivo. The live views provide direct evidence of the changing behavior of GnRH neurons in their different environments, showing that GnRH neurons move with greater frequency and with more changes in direction after they enter the brain. Perturbations of guiding fibers distal to moving GnRH neurons in the nasal compartment influenced movement without detectable changes in the fibers in the immediate vicinity of moving GnRH neurons. This suggests that the use of fibers by GnRH neurons for guidance may entail selective signaling in addition to mechanical guidance. These studies establish a model to evaluate the influences of specific molecules that are important for their migration.


2010 ◽  
Vol 239 (6) ◽  
pp. 1723-1738 ◽  
Author(s):  
N.E. Rawson ◽  
F. W. Lischka ◽  
K.K. Yee ◽  
A.Z. Peters ◽  
E.S. Tucker ◽  
...  

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