The Effect of Neurotoxic Xenobiotics and Exogenous Melatonin on Diurnal Rhythms of Biogenic Amines in Hypothalamic Structures Responsible for LH-RH Production.

2003 ◽  
Vol 2003 (Spring) ◽  
Author(s):  
Andrew Korenevsky ◽  
Gleb Kerkeshko ◽  
Michael Stepanov ◽  
Alexander Arutjunyan
2003 ◽  
Vol 52 (2) ◽  
pp. 77-85
Author(s):  
A. V. Arutjunyan ◽  
М. G. Stepanov ◽  
G O. Kerkeshko ◽  
Е. K. Ailamazyan

Diurnal rhythms of the contents of biogenic amines in the hypothalamus are considered to play an important role in regulation of many functions such as motor activity, feeding behaviour, sleep-awake cycle formation as well as hormonal and immune statuses. Mechanisms of regulation of reproduction that participate in a circadian signal transmission from the suprachiasmatic nuclei (SCN) of the hypothalamus to hypothalamic structures responsible for gonadoliberin (GnRH) synthesis and secretion (the preoptic area - PA, and the medial eminence - ME) are at present being intensively studied. It has been shown that the aging caused disturbances of estrous cycles in female rats are accompanied by a disappearance of diurnal rhythms of activity of monoaminergic and opioid hypothalamic systems playing a key role in regulation of GnRH synthesis and secretion. The experiments carried out have revealed diurnal rhythms of the contents of the studied biogenic amines in the PA, ME and SCN of the hypothalamus. The rhythms are due to the amines increasing in the morning hours when compared to their evening and night levels. The neurotoxic compounds used disturbed the rhythms of the amines. Chronic inhalation of toluene caused a disappearance of the dynamics of all the studied neurotransmitters that was typical of the control group. Meanwhile, a single administration of 1,2-dimethylhydrazine resulted in either a complete disappearance of the diurnal rhythms of the biogenic amines contents found in control, or their phase shifts. Severe disturbances of the GnRH content and of the ROS diurnal dynamics were also observed in the studied hypothalamic areas. The literature allowed supposition that melatonin possessing entraining and antioxidant properties can be used as a protector of disturbances of central mechanisms of regulation of reproduction. However, our experiments have shown that exogenous melatonin does not only eliminate the neurotoxic compounds caused disturbances of diurnal rhythms of the studied indices, but it itself causes deep changes in their dynamics. The effect of melatonin has been found to result in a significant decrease of the catecholamines contents in all the studied hypothalamic structures, particularly of the norepinephrine content, that is accompanied by a profound decrease of the GnRH content and by a disturbance of the diurnal dynamics of reactive oxygen species (ROS) in the PA and ME. The effect of 1,2-dimethylhydrazine on the studied indices was less pronounced when compared to that of melatonin, whereas an injection of the xenobiotic on the background of the pineal gland hormone administration resulted in a predominant effect of the latter. Both the data obtained and the literature review allow to offer a hypothesis for a possible mechanism of involvement of diurnal rhythms of biogenic amines in central regulation of reproduction. It is known that synthesis and secretion of endogenous opioid peptides in the mediobasal hypothalamus undergo diurnal oscillations with minimum in the morning and maximum in the evening and/or at night. The revealed diurnal rhythms of the biogenic amines contents had opposite oscillations. This fact allows a supposition that these rhythms are due to the opioid system activity changing. Both decreased endogenous opioids contents and simultaneously increased morning biogenic amines levels in proestrus can create a neurotransmitter background that is necessary for GnRH surge formation. An evaluation of diurnal rhythms of the biogenic amines contents, GnRH and ROS in the studied hypothalamic structures can be used for an assessment of disturbances of central mechanisms of regulation of reproduction that are caused by other neurotoxic compounds or developed in some diseases and in aging when the functional activity of the pineal gland is altered. The data obtained testify to possible negative side effects of melatonin on hypothalamic regulation of reproduction in therapeutic use of the hormone. The effects of melatonin realized via its receptors are known to highly depend on amplitude of its nocturnal surge and on duration of its increased blood level during a day. Therefore administration of melatonin on the background of its normal synthesis can lead to a number of negative effects due to its increased blood level when compared to its physiological level. Elucidation of the exogenous melatonin caused disturbance of the studied diurnal rhythms of central regulation of reproduction is of great practical use in development of prophylactics helping to eliminate or decrease an effect of damaging factors in unfavourable environmental conditions.


mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Jie Yin ◽  
Yuying Li ◽  
Hui Han ◽  
Jie Ma ◽  
Gang Liu ◽  
...  

ABSTRACT Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.


2019 ◽  
Author(s):  
Jie Yin ◽  
Yuying Li ◽  
Hui Han ◽  
Gang Liu ◽  
Xin Wu ◽  
...  

AbstractMelatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of admistartion of exogenous melatonin on the diurnal variation in gut microbiota in high fat diet (HFD)-fed mice is obscure. Here, we further confirmed the anti-obesogenic effect of melatonin on in mice feed with HFD for two weeks. Samples were collected every 4 h within a 24-h period and diurnal rhythms of clock genes expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm only in the control and melatonin treated mice, but not in the HFD-fed mice. Rhythmicity of these parameters were similar between control and melatonin treated HFD mice compared with the HFD group, indicating an improvement of melatonin in the diurnal clock of host metabolism in HFD-fed mice. 16S rDNA sequencing showed that most microbiota exhibited a daily rhythmicity and the trends differentiated at different groups and different time points. We also identified several specific microbiota correlating with the circadian clock genes and serum lipid indexes, which might contribute the potential mechanism of melatonin in HFD-fed mice. Interestingly, administration of exogenous melatonin only at daytime exhibited higher resistance to HFD-induced lipid dysmetabolism than nighttime treatment companying with altered gut microbiota (Lactobacillus, Intestinimonas, and Oscillibacter). Importantly, the responses of microbiota transplanted mice to HFD feeding also varied at different transplanting times (8:00 and 16:00) and different microbiota donors. In summary, daily oscillations in the expression of circadian clock genes, serum lipid indexes, and gut microbiota, appears to be driven by a short-time feeding of an HFD. Administration of exogenous melatonin improved the compositions and diurnal rhythmicity of gut microbiota, which might be linked to host diurnal rhythm and metabolism.ImportancePrevious studies show that a circadian hormone, melatonin, involves in host lipid metabolism by reprogramming gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of melatonin drinking on the diurnal variation in gut microbiota in high fat diet-fed mice is obscure. Here, we found that 24-h oscillations were widely occurred in circadian clock genes, serum lipid indexes, and gut microbiota. Melatonin drinking improved the compositions and circadian rhythmicity of gut microbiota, which might be linked to host circadian rhythm and metabolism.


1973 ◽  
Author(s):  
Paula Patkai ◽  
Kerstin Pettersson ◽  
Torbjorn Akerstedt

1973 ◽  
Author(s):  
Robert J. Barrett ◽  
Elaine Sanders Bush ◽  
Gerald J. Schaefer ◽  
Michael Germain

2010 ◽  
Vol 01 (03) ◽  
pp. 139-140
Author(s):  
Luise Mansel
Keyword(s):  

Mehr als drei Viertel der Prostata-Karzinome sind Testosteron-sensitiv und wachsen primär hormonabhängig. Daher besteht die Standardtherapie in einer Behandlung mit LH-RH-Analoga (synthetische Gonadotropin-Releasing-Hormon-Analoga). Dabei kommt es durch pharmakologische Absenkung des Serumtestosteronspiegels auf Kastrationsniveau (<50 ng/dl) zur Verringerung der Tumorgröße oder zumWachstumsstillstand. Gegenüber der operativen Kastration hat die medikamentöse Hormonsenkung den Vorteil der Reversibilität.


Sign in / Sign up

Export Citation Format

Share Document