Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.
The unicellular eukaryote Tetrahymena synthesize, store and secrete biogenic amines (histamine, serotonin, epinephrine, dopamine, melatonin) and also can take up amines from the milieu. It also has (G-protein-coupled) receptors (binding sites) for these amines as well, as second messengers. The factors infuencing the mentioned processes are shown. For certain amines the genes and the coded enzymes are demonstrated. The amines influence phagocytosis, cell division, ciliary regeneration, glucose metabolism and chemotaxis. There are interhormone actions between the amines, and between the amines and other hormones produced by Tetrahymena. The critical review discusses the role of amines in the early stages of evolution and compares this to their functions in mammals. It tries to give answer how and why biogenic amines were selected to hormones, and why new functions formed for them in higher ranked animals, preserving also the ancient ones.
The mast cell is a member of the immune system having a basic role in allergic (anaphylactic) reactions. However, it contains, synthesizes, stores and secretes lots of substances, which initiates other reactions or participates in them. These are in connection with the deterioration of tissue correlation, as malignant tumors, angiogenesis, wound healing, pregnancy and different pathological conditions. In addition — as other members of the immune system — mast cells can synthesize, store and secrete hormones characteristic to the endocrine glands and can transport them to the site of requirement (packed transport), or produce and employ them locally. The effect of mast cells is controversial and frequently dual, stimulatory or inhibitory to the same organ or process. This is likely due to the heterogeneity of the mast cells, in morphology and cell content alike and dependent on the actual condition of the targeted tissue. The cells are transported in an unmatured form by the blood circulation and are exposed to microenvironmental effects, which influence their maturation. Their enrichment around tumors suggested using them as targets for tumor therapy more than fifty years ago (by the author), however, this idea lives its renaissance now. The review discusses the facts and ideas critically.
The thymus develops from an endocrine area of the foregut, and retains the ancient potencies of this region. However, later it is populated by bone marrow originated lymphatic elements and forms a combined organ, which is a central part of the immune system as well as an influential element of the endocrine orchestra. Thymus produces self-hormones (thymulin, thymosin, thymopentin, and thymus humoral factor), which are participating in the regulation of immune cell transformation and selection, and also synthesizes hormones similar to that of the other endocrine glands such as melatonin, neuropeptides, and insulin, which are transported by the immune cells to the sites of requests (packed transport). Thymic (epithelial and immune) cells also have receptors for hormones which regulate them. This combined organ, which is continuously changing from birth to senescence seems to be a pacemaker of life. This function is basically regulated by the selection of self-responsive thymocytes as their complete destruction helps the development (up to puberty) and their gradual release in case of weakened control (after puberty) causes the erosion of cells and intercellular material, named aging. This means that during aging, self-destructive and non-protective immune activities are manifested under the guidance of the involuting thymus, causing the continuous irritation of cells and organs. Possibly the pineal body is the main regulator of the pacemaker, the neonatal removal of which results in atrophy of thymus and wasting disease and its later corrosion causes the insufficiency of thymus. The co-involution of pineal and thymus could determine the aging and the time of death without external intervention; however, external factors can negatively influence both of them.
The unicellular ciliate Tetrahymena is a complete organism, one of the most highly developed protozoans, which has specialized organelles performing each of the functions characteristic to the cells of higher ranked animals. It is also able to produce, store, and secrete hormones of higher ranked animals and also react to them. It produces lectins that can bind them and has functions, which are influenced by exogenous lectins. The review lists the observations on the relationship between lectins and Tetrahymena and try to construe them on the basis of the data, which are at our disposal. Considering the data, lectins can be used by Tetrahymena as materials for influencing conjugation, for stimulating hormone receptors, and by this, mimic the hormonal functions. Lectins can influence phagocytosis and movement of the cells as well as the cell division. As Tetrahymena can recognize both related and hostile cells by the help of lectins and surface sugars, it could be surmised a complex predator–prey system. This could determine the survival of the population as well as the nourishment conditions. When Tetrahymena is pathogenic, it can use lectins as virulence factors.
The hormesis concept demonstrates that in contrast to the toxic effect of high doses of materials, irradiation, etc., low doses of them are beneficial and, in addition, help to eliminate (prevent) the deleterious effect of high doses given after it. By this effect, it is an important factor of (human) evolution protecting man from harmful impacts, similarly to the role of immunity. However, immunity is also continuously influenced by hormetic effects of environmental [chemical (pollutions), physical (background irradiations and heat), etc.] and medical (drugs and therapeutic irradiations) and food interactions. In contrast to earlier beliefs, the no-threshold irradiation dogma is not valid in low-dose domains and here the hormesis concept is valid. Low-dose therapeutic irradiation, as well as background irradiations (by radon spas or moderately far from the epicenter of atomic bomb or nuclear facilities), is rather beneficial than destructive and the fear from them seems to be unreasonable from immunological point of view. Practically, all immune parameters are beneficially influenced by all forms of low-dose radiations.
Ah-receptors (AhRs) recognize and bind foreign environmental molecules as well as some target hormones of other nuclear receptors. As ligands activate transcription factors, they transmit the information on the presence of these molecules by binding to the DNA, which in turn activate xenobiotic metabolism genes. Cross talk with other nuclear receptors or some non-nuclear receptors also activates or inhibits endocrine processes. Immune cells have AhRs by which they are activated for physiological (immunity) or non-physiological (allergy and autoimmunity) processes. They can be imprinted by hormonal or pseudo-hormonal (environmental) factors, which could provoke pathological alterations for life (by faulty perinatal hormonal imprinting). The variety and amount of human-made new environmental molecules (endocrine disruptors) are enormously growing, so the importance of AhR functions is also expanding.
Hormones, characteristic to higher ranked animals, are synthesized, stored, and secreted by unicellular eukaryote animals. The unicells also have receptors for recognizing these materials and transmit the message into the cells for provoking response. The hormones are effective in very low concentrations (down to 10–21 M) and opposite effects of lower and higher concentrations can be observed. However, sometimes linear concentration effects can be found, which means that hormesis exists, nevertheless uncertain, as it is in the phase of formation (evolutionary experimentation). Hormesis, by transformation (fixation) of cytoplasmic receptor-like membrane components to receptors in the presence of the given hormone, likely helps the development of unicellular endocrine character and by this the evolution of endocrine system. The effect by extremely low concentrations of hormones had been forced by the watery way of unicellular life, which could establish the physiological concentrations of hormones in the blood of higher ranked animals. This means that hormetic low doses are the normal, effective concentrations and the high concentrations are artificial, consequently could be dangerous.
The unicellular ciliate, Tetrahymena has receptors for hormones of the higher ranked animals, these hormones (e.g. insulin, triiodothyronine, ACTH, histamine, etc.) are also produced by it and it has signal pathways and second messengers for signal transmission. These components are chemically and functionally very similar to that of mammalian ones. The exogenously given hormones regulate different functions, as movement, phagocytosis, chemotaxis, cell growth, secretion, excretion and the cells’ own hormone production. The receptors are extremely sensitive, certain hormones are sensed (and response is provoked) at 10−21 M concentration, which makes likely that the function could work by the effect of hormones produced by the Tetrahymena itself. The signal reception is selective, it can differentiate between closely related hormones. The review is listing the hormones produced by the Tetrahymena, the receptors which can receive signals and the signal pathways and second messengers as well, as the known effects of mammalian hormones to the life functions of Tetrahymena. The possible and justified role of hormonal system in the Tetrahymena as a single cell and inside the Tetrahymena population, as a community is discussed. The unicellular hormonal system and mammalian endocrine system are compared and evolutionary conclusions are drawn.
The unicellular ciliate, Tetrahymena has a complete hormonal system. It has receptors for receiving hormones, produces, stores and secretes hormones, similar to mammalian ones and has signal transduction pathways, for transmitting the information given by the hormones. The first encounter with a hormone provokes the hormonal imprinting under the effect of which the further encounters with the same hormone induces altered (usually enhanced) reaction (hormone binding, hormone synthesis, chemoattraction, movement, growth etc.). The effect of imprinting is durable, it can be observed also after 1000 generations, or after one year in non-dividing cells. Receptors of the nuclear envelope also can be imprinted. The plasma membrane receptors provoked by imprinting are similar to the receptors of mammals. Although steroid hormones are not present in Tetrahymena, the production of them and their receptors can be induced by imprinting. The hormonal imprinting is an epigenetic process and inhibition of DNA-methylation alters the imprinting. Hormonal imprinting in Tetrahymena was likely the first epigenetic phenomenon which was justified at cellular level. It is very useful for the unicells, as it helps to avoid dangerous molecules more easily or to find useful ones and by this contributes to the permanence of the population’s life.