title: Can high maternal melatonin concentrations be responsible for inducing fetal pathologies, and can melatonin participate in immunohormonal homeostasis by determining prohormone convertase activity?--Hypothesis and facts.
abstract: The hypothesis proposed here presents a mechanism of melatonin action, which may explain the role of this neurohormone in the genesis of various human pathologies, including fetal abnormalities. It assumes that monomeric or dimeric forms of indoloderived compounds such as melatonin and precursors of melanin have the ability to selectively stimulate the synthesis of prohormone 1 convertase (PC1) or prohormone 2 convertase (PC2), in proportion to their concentrations in the body. Thus, the mean circadian level of melatonin, by determining the manner and rapidity of proopiomelanocortin (POMC) cleavage, would also determine the mean proopiomelanocortin (POMC) level, maintained in dynamic equilibrium as a result of the simultaneous influence of testosterone, estradiol and cortisol on the intensity of POMC mRNA synthesis. The correlative proportions between the activity of PC1 and PC2 would therefore shape the character of hormonal balance in the organism, and in particular the mean ACTH concentration that determines the level of cyclic adenosine monophosphate (cAMP) concentration in its cells. The hypothesis also suggests that melatonin, by influencing the concentration of ACTH and beta-endorphin and their relative proportion could determine the stimulation or suppression of the immune system, thereby confirming its role as an immunomodulator. A disturbance in the above model of immunohormonal equilibrium, resulting from, for example, decreased pineal efficiency, would lead to stimulation of an alternative mode of achieving homeostasis, i.e. increase in concentration of melanin monomers and dimers, with concomitant high activity of tyrosine kinase and high cyclic guanosine monophosphate (cGMP) concentration in the cells. According to the proposed hypothesis, the risk of bearing a developmentally handicapped child would be highest in a woman with a high circadian secretion of melatonin, i.e. with domination of melatonin dimers and high PC1 activity, a condition which may be additionally aggravated by the exposure of the mother to adverse environmental factors or by immunohormonal disturbances. The hypothetical break-up of maternal melatonin dimers when crossing placenta would be the cause of excessive concentration of melatonin monomers and high PC2 activity in the fetus, and thus it should be the reason for very low levels of vimentin filaments and cAMP concentration in embryonal cells, the latter being directly responsible for inducing fetal pathologies.
authors.affiliation: Department of Endocrinology, Sterling's Hospital, Medical University of Lódź, Poland. ciesla@bgamld.bg.am.lodz.pl
authors.forename: W
authors.initials: W
authors.lastname: Ciesla
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology*; D005260:Female; D005315:Fetal Diseases / Q000209:etiology*; D045683:Furin; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D008431:Maternal-Fetal Exchange; D008543:Melanins / Q000378:metabolism; D008550:Melatonin / Q000276:immunology / Q000378:metabolism*; D010870:Pineal Gland / Q000378:metabolism; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000276:immunology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013381:Subtilisins / Q000276:immunology / Q000378:metabolism*
chemical_list: D008543:Melanins; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D013381:Subtilisins; D045683:Furin; D008550:Melatonin