scholarly journals Impaired hypothalamic regulation of reproductive function when exposed to neurotoxic compounds and melatonin

2003 ◽  
Vol 52 (2) ◽  
pp. 77-85
Author(s):  
A. V. Arutjunyan ◽  
М. G. Stepanov ◽  
G O. Kerkeshko ◽  
Е. K. Ailamazyan
Keyword(s):  
Pineal Gland ◽  
Biogenic Amines ◽  
Blood Level ◽  
Female Rats ◽  
Diurnal Rhythms ◽  
Central Regulation ◽  
Exogenous Melatonin ◽  
Diurnal Dynamics ◽  
Regulation Of Reproduction ◽  
Hypothalamic Regulation

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.

scholarly journals Role of bio-genic amines for the hypothalamic regulation of reproductive function

2004 ◽  
Vol 53 (1) ◽  
pp. 98-106
Author(s):  
A. V. Arutiunian ◽  
G. О. Kerkeshko ◽  
М. G. Stepanov ◽  
А. V. Korenevskiy ◽  
Е. К. Aylamazian
Keyword(s):  
Reproductive Function ◽  
Diurnal Rhythms ◽  
Central Regulation ◽  
Suprachiasmatic Nuclei ◽  
Regulation Of Reproduction ◽  
Secretion Regulation ◽  
Hypothalamic Regulation ◽  
Reproductive Cycles ◽  
Central Oscillator

The present review is dedicated to monoaminergic systems involved in hypothalamic regulation of reproduction, as well as to the role of the systems in GnRH synthesis and secretion regulation. Data are presented on the ovarian steroid hormones, the suprachiasmatic nuclei of the hypothalamus, in which the central oscillator of a mammalian organism's diurnal rhythms is located, and on the pineal hormone melatonin involved in formation of reproductive cycles. Both own results and literature data referring to the role of diurnal rhythms of the activity of monoaminergic systems of the hypothalamus in the central regulation of reproduction are discussed.

Hypothalamic regulation of reproduction under the chronic influence of toluene and melatonin

2021 ◽  
Vol 50 (2) ◽  
pp. 42-46
Author(s):  
G. O. Kerkeshko
Keyword(s):  
Biogenic Amines ◽  
Preoptic Area ◽  
Chronic Administration ◽  
Female Rats ◽  
Control Group ◽  
Simultaneous Administration ◽  
Chronic Effect ◽  
Circadian Variations ◽  
Hypothalamic Regulation ◽  
Maximal Permissible Concentration

Experiments on chronic administration of melatonin with and without chronic inhalation of toluene dosed at both maximal permissible concentration (50 mg/ml) and limited chronical range (500 mg/m3) have been carried out on female rats to discover their effects on biogenic amines system in hypothalamic structures related to gonadoliberin synthesis and secretion - preoptic area (PA) and median eminence (ME). Contents of biogenic amines in ME and especially in PA have been shown to have circadian variations with maximum in the morning in control group of rats.The chronic effect of synchronizing agent melatonin (administered dissolved in drinking water in concentration of 10 pg/m l, at night during 2 months) on neotransmitters and their circadian variations in both hypothalamic structures proved surprisingly to be much alike the effect of toluene. Both chemicals cause the disturbances of normal circadian variations o f norepinephrine, dopamine and serotonine in PA and dopamine in ME. The simultaneous administration of toluene and melatonin showed likewise no synchronizing ability of the latter under the conditions described.

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
Keyword(s):  
Biogenic Amines ◽  
Diurnal Rhythms ◽  
Exogenous Melatonin ◽  
Lh Rh

scholarly journals Experimental study of mechanisms of disturbances of hypothalamic regulation of reproduction

2005 ◽  
Vol 54 (1) ◽  
pp. 57-63
Author(s):  
A. V. Arutjunyan ◽  
G. О. Kerkeshko ◽  
М. G. Stepanov ◽  
А. V. Korenevsky ◽  
Е. К. Ailamazyan
Keyword(s):  
Experimental Data ◽  
Experimental Study ◽  
Sex Steroids ◽  
Circadian Oscillator ◽  
Diurnal Rhythms ◽  
Regulation Of Reproduction ◽  
Hypothalamic Regulation ◽  
Negative Effect ◽  
Rfbr Grant ◽  
Reproductive Cycles

Summary: Diurnal rhythms of the activity of a number of monoaminergic systems of the hypothalamus (norepinephrine and serotonin in PA and ME-ArN, as well as dopamine in ME-ArN) have been shown to depend on the functioning of an endogenous circadian oscillator in SCN of the hypothalamus. Light modifies the diurnal rhythms of the neurotransmitters. Enhancement of the activity of the noradrenergic systems with sex steroids in proestrus is an important mechanism of the forming of the preovulatory surge of GnRH and gonadotropines secretion, which initiates ovulation. Consideration of our own experimental data and literature allow the supposition that the change of diurnal rhythms of norepinephrine in PA and ME-ArN could result in profound disturbances of hypothalamic regulation of reproductive cycles and be one of key reasons for negative effect of xenobiotics on reproduction. Supported by RFBR grant 04-04-49204.

Monosodium glutamate administration early in life alters pineal melatonin nocturnal profile in adulthood

2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Pineal Gland ◽  
Serum Insulin ◽  
Monosodium Glutamate ◽  
Female Rats ◽  
Pineal Melatonin ◽  
Melatonin Synthesis ◽  
Male And Female Rats ◽  
Melatonin Production

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.

PHYSIOLOGICAL EFFECTS OF THE PINEAL GLAND IN ANDROGEN-STERILIZED FEMALE RATS

1970 ◽  
Vol 63 (4) ◽  
pp. 667-678 ◽  
Author(s):  
Russel J. Reiter
Keyword(s):  
Pineal Gland ◽  
Reproductive Organs ◽  
Female Rats ◽  
Inhibitory Influence ◽  
Light Deprivation ◽  
Vaginal Smears ◽  
Adult Rats ◽  
Androgen Treatment ◽  
Postnatal Treatment ◽  
Cervical Ganglia

ABSTRACT The influence of early androgen treatment, light deprivation (by blinding), pinealectomy and superior cervical ganglionectomy on the reproductive system of female rats was tested. Early postnatal treatment of rats with testosterone propionate caused adult rats to exhibit the characteristic signs of androgen sterilization; these included polyfollicular ovaries, normal-sized uteri and persistent vaginal cornification. If early androgentreated rats also were blinded the ovaries were smaller in size and contained fewer follicles, the uteri were greatly reduced in size and the incidence of vaginal oestrus was decreased by approximately 50% If in addition to blinding, androgen-sterilized animals were subjected to either removal of the pineal gland or superior cervical ganglia, the reproductive organs and the vaginal smears were indistinguishable from those of testosterone-treated rats with eyes. These data indicate that the inhibitory influence of blinding on the pituitary-ovarian axis was mediated through the sympathetic nervous system and the pineal gland. The restraining influence of light deprivation on the growth of the reproductive organs was not permanent as illustrated by the fact that if these animals were kept to 120 days of age the ovaries and uteri grew to the same level as those of pinealectomized control rats.

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz
Keyword(s):  
Body Weight ◽  
Reproductive System ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Control Groups ◽  
Melatonin Treatment ◽  
Exogenous Melatonin ◽  
Reproductive Axis ◽  
Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

scholarly journals DEPRESSED PITUITARY PROLACTIN LEVELS IN BLINDED ANOSMIC FEMALE RATS: ROLE OF THE PINEAL GLAND

Reproduction ◽  
1972 ◽  
Vol 31 (1) ◽  
pp. 159-162 ◽  
Author(s):  
R. J. DONOFRIO ◽  
R. J. REITER
Keyword(s):  
Pineal Gland ◽  
Female Rats ◽  
Pituitary Prolactin

Circadian rhythms in blinded rats: correlation between pineal and activity cycles

1978 ◽  
Vol 234 (3) ◽  
pp. R110-R114
Author(s):  
C. R. Pohl ◽  
F. P. Gibbs
Keyword(s):  
Pineal Gland ◽  
Activity Rhythm ◽  
Diurnal Rhythms ◽  
Light Cycle ◽  
Activity Phase ◽  
Running Activity ◽  
Free Running ◽  
Activity Cycles ◽  
Rat Pineal Gland ◽  
Sampling Times

The rat pineal gland exhibits diurnal rhythms in levels of N-acetyltransferase activity and its substrate serotonin. We attempted to demonstrate the endogenous nature of these changes by measuring the pineal enzyme and its substrate in rats blinded for 37 and 60 days. In order to determine the proper sampling times for these one-time, terminal measurements, the running activity rhythm of each rat was monitored continuously and the animals were killed at either midrest or midrun. Circadian changes of pineal N-acetyltransferase and serotonin were demonstrated, with enzyme levels high and substrate content low during midrun. Absolute values during each activity phase were similar to those of control rats entrained to a light cycle (LD 12:12). Levels of the pineal constituents were unrelated to local time. These results suggest that rats blinded for up to 60 days maintain their free-running pineal rhythms with undamped amplitudes and in synchronization with the activity rhythm.

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