Can melatonin regulate the expression of prohormone convertase 1 and 2 genes via monomeric and dimeric forms of RZR/ROR nuclear receptor, and can melatonin influence the processes of embryogenesis or carcinogenesis by disturbing the proportion of cAMP and cGMP concentrations? Theoretic model of controlled apoptosis.
The presented model of controlled apoptosis has been based on the assumption that correct information exchange between an organism as a whole, and each of its cells is conditioned by mutual proportions of cAMP and cGMP concentrations (CcAMP, CcGMP), according to the formula CcAMP x CcGMP = 'a' (constant). The regulation of balance of these 'second messengers' in a cell and an extracellular space would depend on the mutual proportions of concentrations of Melatonin and monomers of Melanin. These indoloderived compounds could be the activators of the transcription factors i.e. RZR and NFkappa-B, regulating the expression of Prohormone Convertase (PC) gen and Nitric Oxide Synthase (NOS) gen, respectively. Additionally, maternal Melatonin and Nitric Oxide (NO), being able to pass through trophoblast or placenta freely, would play decisive role in the synchronization of embryogenesis and intrauterine development of the fetus. In case of an embryo or a fetus, the result of CcAMP and CcGMP multiplication, different from the proper constant 'a'-value, would mean occurrence of disorders in the structure and functioning of the cellular tensegrity system and, in consequence, disturbances in the intercellular information exchange. It would lead to deviation in cellular metabolism, oriented cell movement, uncontrolled apoptosis, and as a consequence, would lead to the development of fetal defects. In case of a child or an adult, a sudden occurrence and prolongation of such disturbances in CcAMP-CcGMP proportions would induce a process of apoptosis of normal cells and an initiation of a cancerogenesis. On the other hand, the recovery of equilibrium in the information exchange system would initiate apoptosis of neoplastic cells, and simultaneously, proliferation of connective tissue cells. According to the presented hypothesis, a decrease in CcAMP and destabilization of the CcAMP-CcGMP balance in an embryo or a fetus would result from relatively excessive amounts of maternal Melatonin (monomers) in fetal circulation, while a decrease of CcAMP and destabilization of the CcAMP-CcGMP balance in a child or an adult would be a consequence of relatively insufficient amounts of Melatonin (dimers) in an organism. It seems possible, that determination of both CcAMP and CcGMP would enable an early detection of high risk of developmental defects occurrence in an embryo or a fetus and neoplastic processes in a child or an adult. This method might also be considerably useful in monitoring a safe substitutional hormonotherapy.
Cieśla
W
W
Department of Physiology, Institute of Physiology and Biochemistry, Medical University of Łódź, Sterling's Hospital, Endocrinology Unit, National Clinic Hospital No 3, Łódź, Poland. ciesla@bgamld.bg.am.lodz.pl
D017209:Apoptosis / Q000502:physiology*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D019281:Dimerization; D005314:Embryonic and Fetal Development / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008550:Melatonin / Q000502:physiology*; D008962:Models, Theoretical; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D044094:Receptors, Melatonin; D013381:Subtilisins / Q000235:genetics*
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D000242:Cyclic AMP; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; D006152:Cyclic GMP; D008550:Melatonin