ABSTRACT
Industrial xenobitics, as well as endogenous damaging factors, such as L-homocysteine, are a well-known source of reactive oxygen species that disrupt biological processes. Among many others, luteinizing hormone releasing hormone synthesis and secretion mediated by a variety of neurotransmitters, which are under control of the hypothalamus and pineal gland, may be put in peril by reactive oxygen species. Their formation can be one of the reasons for the reproductive function shutdown in ageing as the generic response to the damaging factors independent of their nature. We review recent findings demonstrating the role of reactive oxygen species in disrupting the circadian signal originated in the main pacemaker of the organism, the suprachiasmatic nuclei of the hypothalamus, on its way to the hypothalamic areas responsible for the luteinizing hormone preovulatory surge.
Subject(s)
Aging, Premature/etiology , Aging, Premature/metabolism , Reactive Oxygen Species/metabolism , Reproduction/physiology , Animals , Female , Humans , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Melatonin/metabolism , Melatonin/pharmacology , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Neurotoxins/metabolism , Neurotoxins/toxicity , Reproduction/drug effectsABSTRACT
Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging. The investigation of epithalamine (a polypeptide preparation from the bovine pineal gland) effect on circadian rhythms disturbed by the neurotoxic compound DMH has shown a recovery of the diurnal dynamics of NE in MPA. In addition, NE was found to decrease from 9:30 till 11 o'clock, Circadian Time (CT), which was typical of control animals. Epitalon (Ala-Glu-Asp-Gly) proved to be more effective in ME-Arc. This peptide prevents the xenobiotic caused disturbance of DA diurnal rhythm, keeping this metabolite low at 5 o'clock (CT) with it having increased by 11 o'clock (CT). The data obtained suggest that the pineal gland is important for the circadian signal normalization needed for gonadoliberin surge on the day of proestrus. Melatonin and peptides of the pineal gland can be considered as effective protectors of female reproductive system from xenobiotics and premature aging.
