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The influence of dietary (n-3) compared with (n-6) polyunsatured fatty acids (PUFA) on the lipid composition and metabolism of adipocytes was evaluated in rats over a period of 1 week. Isocaloric diets comprised 16.3 g/100 g protein, 53.8 g/100 g carbohydrate and 21.4 g/100 g lipids, the latter containing either (n-3) PUFA (32.4 mol/100 mol) or (n-6) PUFA (37.8 mol/100 mol) but having identical contents of saturated, monounsaturated and total unsaturated fatty acids and identical polyunsaturated to saturated fatty acid ratios and double bond indexes. Despite comparable food intake, significantly smaller body weight increments and adipocyte size were observed in rats of the (n-3) diet group after feeding for 1 wk. Rats fed the (n-3) diet also had significantly lower concentrations of serum triglycerides, cholesterol and insulin compared with those fed the (n-6) diet, although levels of serum glucose and free fatty acids did not differ in the two dietary groups. In the (n-6) diet group, the (n-6) and (n-3) PUFA contents of plasma triglycerides, free fatty acids and phospholipids were 30-60% higher and 60-80% lower, respectively, than in the (n-3) diet group, whereas adipocyte plasma membrane phospholipids showed a significantly higher unsaturated to saturated fatty acid ratio and greater fluidity. Glycerol release in response to noradrenaline was significantly higher in the adipocytes of rats fed the (n-3) diet, whereas the antilipolytic effect of insulin generally did not differ in the two groups. Finally, insulin stimulated the transport of glucose and its incorporation into fatty acids to a lesser extent in adipocytes of (n-3) diet fed rats compared with (n-6) diet fed rats. This reduction in the metabolic effects of insulin in rats fed a (n-3) diet for 1 wk could be related to smaller numbers and a lower binding capacity of the insulin receptors on adipocytes and/or to a lesser degree of phosphorylation of the 95 kDa beta subunit of the receptor. In conclusion, dietary intake for 1 wk of (n-3) rather than (n-6) PUFA is sufficient to induce significant differences in the lipid composition and metabolic responses to insulin of rat adipocytes. [ABSTRACT FROM AUTHOR]

In recent years it was disclosed, that numerous organotin(IV) derivatives have remarkable cytotoxicity against several types of cancer cells. The property to inhibit cell growth makes these compounds promising for antitumor therapy, as the clinical effectiveness of cisplatin is limited by drug resistance and significant side effects. Tributyltin and triphenyltin are known as endocrine disruptors. Moreover, the compounds exert their toxicity in mammals predominantly through nuclear receptor signaling. Here we present the effects of tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) on cell proliferation, expression of proapoptotic p53, Bax, and antiapoptotic Bcl-2 proteins in human breast cancer MCF-7 cell line. Dose and time dependent (24, 48 and 72 h) cell expositions have demonstrated TBT-Cl as more effective in inhibiting MCF-7 cell proliferation than TPT-Cl. Short time treatment with TBT-Cl displayed marked stimulation of p53 protein expression when compared to TPT-Cl. Both organotin compounds displayed similar mild enhancement of Bax protein expression. The 24h exposition of TPT-Cl induced substantial diminution of Bcl-2 protein expression in comparison with both, untreated cells and TBT-Cl treated cells. Our observations indicate that TBT-Cl and TPT-Cl have different antiproliferative potency and distinct impact on expression of apoptosis marker proteins., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Staphylea has been used for long time in Traditional Chinese Medicine (TCM) and by Native Americans in a number of therapeutical indications. The present study describes in vitro antiproliferative, cytotoxic properties (MTT and LDH test) and antioxidant activities (reduction of DPPH radical and peroxynitrite radical) of Staphylea colchica Stev. (SC), S. elegans Zab. (SC), S. holocarpa Hemsl. (SH) and S. pinnata L. (SP) leave water extracts. Time- (24 and 72 h) and dose- (1-150 microg/mL) dependent effects of the above extracts were tested at the mitochondrial (MTT test) and plasma membrane level (LDH leakage) in A431 human skin carcinoma cells. Screening of these properties has shown time and dose dependent increase of harmful effects, the highest activity was observed for the SE, while the less active was the SH extract. The ED(50) values for the mitochondrial and membrane damage were nearly identical for the SE and very similar for SH extract. These findings indicate simultaneous injury of both cell compartments by SE and SH extracts. The highest antioxidant potential of SE species is accompanied by the highest content of flavones/flavonols and polyphenols. Only flavonoid contents are associated with antiproliferative effects and cell membrane injury, while antioxidant properties are the result of polyphenol content. The data clearly demonstrate that individual Staphylea L. species differ, not only in the amount of biologically active compounds, but also by the extent of harmful and beneficial effects.

Objective: Alcohol intake is known to interfere with endocrine system functions thus inducing hormonal and metabolic imbalance. The aim was to investigate the impact of chronic intake of mild alcohol concentration on serum leptin, adiponectin and resistin and their gene expression in epididymal adipose tissue (EAT) of rats., Methods: The 28 days study was based on 3 experimental groups of adult male Wistar rats: 1/ ad libitum intake of 6 % ethanol solution and pelleted diet (A), 2/ pair fed animals (PF) fed pelleted diet in the same caloric amount as A rats on previous day (alcohol+diet), 3/ control rats (C) with unrestricted intake of water and pelleted diet. RT-PCR method was used for determination of adipokines gene expression in epididymal adipose tissue, serum levels were measured by ELISA kits., Results: The animals of A group were characterized by reduced food and energy intake (-10 % vs C), lower body mass gain, reduced epididymal fat mass with smaller adipocytes. Alcohol consumption significantly increased glycemia, serum insulin was not affected. The raise of NEFA in A and PF rats gives the evidence of intensified lipolysis due to the deficiency of energy intake. Alcohol consumption significantly increased serum leptin and resistin, elevated adiponectin was present in A and PF rats. In parallel with increased serum levels the expression of adiponectin gene in epididymal adipose tissue was elevated in the same A and PF rats. Leptin and resistin mRNA levels were similar as in C regardless of alcohol intake or pair-fed feeding. Increased leptin and resistin levels positively correlated with glycemia and negatively with the size of adipocytes. Elevated serum leptin and resistin together with high adiponectin after chronic moderate alcohol intake could contribute to alteration of energy metabolism either individually or in reciprocal coordination., Conclusions: 28 days consumption of 6 % ethanol solution changed the nutritional status of rats and induced significant elevation of serum leptin and resistin, while elevated gene expression in epididymal adipose tissue was proved for adiponectin only. Elevated serum adipokines could contribute to increased glycemia and altered glucose homeostasis.

Some kojic acid (KA) derivatives and selenium containing compounds possess antiproliferative properties. The present study tested novel selenocyanatomethyl derivatives of KA for growth inhibitory and LDH cytotoxic activities. Human skin carcinoma (A431) and human breast carcinoma (MCF7) cells were treated with 5-benzyloxy-2-selenocyanatomethyl-4-pyranone (P763) and 5-methoxy-2-selenocyanatomethyl-4-pyranone (P764) in selected concentrations for 24, 48 and 72 h. Cell viability tests aimed at intracellular injury of mitochondria (MTT) and lysosomes (neutral red uptake, NR) revealed (a) higher growth inhibitory activity of the benzyloxy-selenocyanatomethyl derivative of KA (P763) compared with the methoxy derivative (P764) in both cell lines, (b) an intensified effect with time of exposure (MTT test only). The results demonstrate that NR cell survival/viability assay is more sensitive than the MTT test to detect subcellular changes induced by test compounds. Cell membrane integrity determined by LDH leakage confirmed an exaggerated cytotoxic effect of P763 but similar sensitivity of both cell lines to membrane injury. The ED50 values for all three tests used indicate that injury of intracellular mitochondria and lysosomes precedes the loss of membrane integrity. Cell growth inhibitory activities of new selenium containing kojic acid derivatives are preferentially aimed at the intracellular compartment rather than the plasma membrane and enlarge the group of antiproliferative active compounds., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to compare the changes in plasma levels of hormones involved in modulation of the immune system function after exposure to stress in two rat strains with different susceptibility to immunoantigens., Methods: Adult rat males of Lewis (LEW) and Fischer 344 (FIS) strains were exposed to restrain stress for 2 hours and blood samples were collected during stress exposure. Other groups of animals were exposed to restrain stress for 2 hours and sacrificed 3 hours later for blood and organ collection. Corticosterone, testosterone, dehydroepiandrosterone, 17beta-estradiol and progesterone were estimated by radioimmunoassay, epinephrine and norepinephrine levels were determined by radioenzymatic method., Results: The levels of plasma corticosterone and catecholamines were significantly higher during stress exposure in FIS as compared to LEW rats. Greater decrease of testosterone levels and higher levels of estradiol were noted after exposure to stress in LEW rats. Higher values of progesterone plasma levels were noted in FIS rats after stress., Conclusions: These results demonstrated the differences in the response of catecholamines, adrenal and gonadal steroids after exposure to stress in LEW and FIS rats with lower levels of hormones with anti-inflammatory action in LEW rats.

White adipose tissue (WAT) is now recognized as a highly active metabolic tissue and important endocrine organ producing numerous peptides and proteins with broad biological activity. The term adipokines has been coined to refer to a series of adipocyte-derived biologically active molecules, which may influence the function as well as the structural integrity of other tissues. Adipokines are implicated in control of food intake, energy balance and body weight (leptin), glucose homeostasis (e.g., adiponectin, resistin, adiponutrin), lipid metabolism (e.g., retinol-binding protein, cholesterolester transfer protein), angiogenesis (vascular endothelial growth factor VEGF), fibrinolytic system (plasminogen activator inhibitor-1 PAI-1), pro- and anti-inflammatory effects (e.g., tumor necrosis factor-alpha TNF-alpha, interleukin-6 IL-6) or sexual development and reproduction (leptin). Alterations of WAT mass in obesity or lipoatrophy effect the production of most adipose secreted factors. Besides others, alcohol consumption affects also hormonal system leading to non-physiological increase/decrease of hormone gene expression and plasma hormone concentrations appearing as final poor or stronger effects on target tissues. As mentioned above, white adipose tissue is important endocrine organ, so alcohol intake can alter also adipokines expression in WAT and adipokines plasma levels and in this way it can affect the adipokine-targeted tissues and their functions.

Philadelphus coronarius L. is big, leggy and deciduous old-fashioned shrub known for its fragrant white flowers in the late spring. Some members of genus Philadelphus L. are known for their antibacterial, antiradical and immunomodulatory effects. Therefore, these herbs represent prospective sources for the isolation of active substances with desired effects. We have investigated the cytotoxicity effects of water extracts from leaves and branches of Philadelphus coronarius L. (Hydrangeaceae). A431 cells (human skin carcinoma cell line) and the human breast adenocarcinoma cell line (MCF-7) were treated with various doses of individual extracts (0,1-100 microg dry matter/ml) for 24 h and 72 h. The highest toxic effects of both plant parts extracts were observed on MCF-7 cells regardless the time of treatment. Cells A431 were less sensitive to toxic effects of leaves and branches extracts but the time dependence was present with the tendency of increased toxicity after chronic treatment. There were no differences in the extent of toxic effects between branches and leaves extracts. The results obtained so far will provide the basis for the future studies with isolated active substances from these extracts.

Steroidogenesis, expansion of oocyte-cumulus complex, and meiotic maturation of the oocyte represent intrafollicular processes taking important part in the background of successful fertilisation. The reproductive health of female could be affected by a number of endogenous as well as exogenous factors, such as exposure to agents from specific lifestyle habits, environmental pollutants with endocrine disrupting properties, or heavy metals. Published data indicate that exposure to chemicals may cause alterations in reproductive behavior and contribute to sub-fecundity, infertility, or ovarian failure. Female reproductive functions can be compromised by exposure to toxic chemicals at a variety of sites, including ovary or reproductive tract. Substantial harmful effects of cigarette smoke on fecundity and reproduction have become apparent but are not generally appreciated. The effects of cigarette smoke components (cadmium, nicotine, cotinine) absorbed into the organism on intrafollicular processes may thus in part explain the negative impact of smoking on female fertility. Moreover, it is now evident that a variety of man-made pollutants present in the environment are capable to disrupt normal endocrine function in many species. Examples of these "endocrine disrupters" include plasticizers, such as phthalates and bisphenol A. The effects of selected environmental chemicals on the processes of steroidogenesis, expansion of oocyte-cumulus complex, and meiotic maturation of the oocyte are summarized in the present paper and possible mechanisms of action of these agents are suggested. However, for complete understanding the mechanisms by which chemical agents from the environment can affect the intrafollicular processes, a lot of further investigation is needed.

Receptor tyrosine kinases have a single transmembrane (TM) segment that is usually assumed to play a passive role in ligand-induced dimerization and activation of the receptor. However, mutations within some of these receptors, and recent studies with the epidermal growth factor (EGF) and ErbB2 receptors have indicated that interactions between TM domains do contribute to stabilization of ligand-independent and/or ligand-induced receptor dimerization and activation. One consequence of the importance of these interactions is that short hydrophobic peptides corresponding to these domains should act as specific inhibitors. To test this hypothesis, we constructed expression vectors encoding short fusion peptides encompassing native or mutated TM domains of the EGF, ErbB2, and insulin receptors. In human cell lines overexpressing the wild-type EGF receptor or ErbB2, we observed that the peptides are expressed at the cell surface and that they inhibit specifically the autophosphorylation and signaling pathway of their cognate receptor. Identical results were obtained with peptides chemically synthesized. Mechanism of action involves inhibition of dimerization of the receptors as shown by the lack of effects of mutant nondimerizing sequences, completed by density centrifugation and covalent cross-linking experiments. Our findings stress the role of TM domain interactions in ErbB receptor function, and possibly for other single-spanning membrane proteins.

Simultaneously with human space flights several series of observations were performed by using experimental animals--mainly rats--exposed to space flights on board of special satellites BION-COSMOS or in Shuttle Transportation Systems (STS). The aims of these experiments were to study in more details: the mechanisms of the changes in bones and skeletal muscle, the alterations of the function of immune system, the radiation effects on organism, the mechanism of the changes of endocrine functions, the evaluation of the role of hormones in alteration of metabolic processes in organism. The advantages of these animal experiments were the possibilities to analyze not only the plasma samples, but it was possible to obtain samples of organs or tissues: for morphological and biochemical analysis for studies of the changes in enzyme activities and in gene expressions, for measurement of metabolic processes and for investigation of the hormone production in endocrine glands and estimation of the response of tissues to hormones. It was also possible to compare the endocrine response to spaceflight and to other stress stimuli. These animal studies are interesting for verification of some hypothesis in the mechanism of adaptation of human organism to the changes of gravity. The disadvantage was, however, that the animals in almost all experiments could be examined only after space flight. The actual inflight changes were investigated only in two SLS flights. In this short review it is not possible to evaluate all hormonal data available on the response of endocrine system to the conditions of space flights. Therefore we will concentrate on the response of pituitary adrenocortical system, pituitary thyroid and pituitary gonadal functions.

This minireview summarizes the results of the observations on changes in endocrine functions of rats exposed to space flights for various periods. The results found after space flights are compared with those obtained from rats in acute or repeated restrain stress. A slight increase of plasma catecholamine levels was observed in rats after space flight of longer duration (>14 days), but no changes in catecholamine content in the activity of catecholamine synthesizing enzymes were noted in adrenal medulla and in hypothalamus. The norepinephrine content was, however, decreased in several nuclei selected from hypothalamus of flight rats. Plasma corticosterone levels were increased after space flight and morphological examination of pituitary showed elevated activity of corticotrophs. However, the plasma levels of ACTH were not increased in rats 6 hours after space flight. These changes in plasma hormone levels affected the activity of enzymes involved in metabolism of amino acids in liver and lipolysis in adipose tissue. The plasma levels of testosterone and triiodothyronine were diminished after space flight suggesting the suppression of the thyroid and gonadal activity. Increase of plasma insulin and glucose levels were found in rats after space flight, but the glucagon values were not changed. Comparing these results from flight rats with the animals exposed to acute or repeated stress indicate that long stay in microgravity do not represent very intensive stressogenic stimulus for adrenocortical and sympatho-adrenomedullar systems, and hormone alterations observed after space flight may be due to acute gravitational stress resulting from a return to Earth gravity. Therefore further studies including the inflight animal experiments on a board of International Space Station are necessary for elucidation of the effects of microgravity on endocrine functions.

Objective: To test the effects of novel oral hypoglycemic agent A-4166 on lipolysis and lipogenesis in adipocytes from normal rats and non-obese, hypertriglyceridemic, insulin resistant and hypertensive rats (HTG) fed basal or high fat diet., Methods: Adult male Wistar rats and hereditary HTG rats (from our own colony) were used. They were fed either basal or high fat diet for three weeks. On the day of observation the active substance A-4166 was administered intragastrically by gavage 30 minutes before decapitation. Blood was collected for the determination of insulin, glycemia, non esterified fatty acids (NEFA) by using commercial kits. The isolated adipocytes were prepared from epididymal fat pads and lipolysis (by measurement of glycerol release) and lipogenesis (by estimation of labeled glucose incorporation into lipids) were determined., Results: The administration of A-4166 results in increased serum insulin and decreased serum glucose level in all rats irrespective of the diet. A significant diminution of serum NEFA levels was observed in A-4166 administered Wistar and HTG rats fed high fat diet. In both groups of rats fed basal diet the lipolysis was not affected by A-4166. However, a decrease of lipolysis was found after A-4166 in Wistar rats fed high fat diet. The stimulation of lipolysis by norepinephrine was not influenced by A-4166. A lowered basal lipolysis was found in HTG rats fed high fat diet. The stimulation of lipolysis by norepinephrine was diminished in HTG rats as compared to Wistar animals. Administration of A-4166 did not affect the stimulation of lipolysis by norepinephrine in HTG rats. A decrease of stimulatory action of insulin on lipogenesis was found in Wistar rats fed high fat diet and in all groups of HTG rats. The administration of A-4166 did not change the basal lipogenesis and also the effect of insulin on lipogenesis., Conclusions: Besides the hyperinsulinemic and hypoglycemic effect of A-4166 also an influence on nonesterified fatty acid serum levels was observed in rats fed high fat diet. This can be partially explained by an antilipolytic action of hyperinsulinemia after A-4166. The studies of lipogenesis showed that Wistar rats fed high fat diet and HTG animals are resistant to the stimulatory action of insulin on lipogenesis and that administration of A-4166 did not affect this response to insulin.

Tedisamil is antiarrhythmic class III drug with antifibrillating/defibrillating potency linked to enhancement of intermyocyte gap junctional electrical coupling most likely via its sympathomimetic cAMP-related mechanisms. This study was designed to examine the effect of tedisamil on cAMP level in guinea pig hearts in vivo and in vitro in Langendorff preparation. The drug was administered either as a bolus into vena jugularis in dosage 1.0 and 1.5 mg/kg or into the perfusion solution at a concentration of 1.5 x 10(-6) mol/l. In additional experiments, this period was followed by brief 10 min global ischemia, induced by clamping of the aorta or perfusion. After 10 min from the onset of tedisamil administration as well as after 10 min of ischemia the ventricular tissue was immediately frozen for cAMP immunoassay. Tedisamil caused in normal heart small but significant dose-dependent increase of myocardial cAMP (pmol/mg) level in vivo 1.8 and 2.5 vs. 1.4 as well as in vitro 1.1 vs. 0.8 (p < 0.05) conditions. Ischemia itself induced accumulation of cAMP in both, in vivo and in vitro experiments, 2.6 vs. 1.4 and 1.3 vs. 0.8, respectively. The preischemic elevation of cAMP by tedisamil was not potentiated by following ischemia, on the contrary, decline of the cyclic nucleotide was detected comparing to ischemia itself. In conclusion, tedisamil increased cAMP level in normal heart and prevented additional ischemia-related elevation of this nucleotide. The results indicate modulation of myocardial cAMP level by tedisamil, which may account for its protective effect on gap junctional electrical coupling.

Objective: To study the basal and ACTH stimulated production of corticosterone by adrenal cortex on one hand and the binding and degradation of corticosterone in the liver of adult rats which were treated with monosodium glutamate (MSG) during the neonatal period., Methods: Male offsprings of Sprague-Dawley rats were injected i.p. with MSG (4 mg/g of b.w. in saline) on alternated days for the first 10 days of life, their littermates being used as controls. On the 21st postnatal day they were weaned and used for the observation at the age of 65-75 days. After sacrifice the level of corticosterone in serum and the release of corticosterone from incubated adrenals under basal and ACTH stimulated conditions (ACTH in 6 concentrations from 1.25 to 80 mU/ml medium) were estimated. In addition, glucocorticoid binding to cytosol receptors in the liver and muscle tissues was determined. Corticosterone degradation rate was measured by decrease of corticosterone concentration added to the medium after the incubation with liver slices., Results: Adult rats neonatally treated with MSG had reduced weight of adrenal glands, while plasma corticosterone levels and its basal production by adrenals in vitro were significantly higher than in controls. In MSG treated rats the stimulation of corticosterone production by ACTH was diminished. Glucocorticoid binding to liver cytosolic receptors was significantly decreased, while that in muscle tissue was only slightly elevated. Moreover, a decreased corticosterone degradation rate in liver slices was observed in rats treated neonatally with MSG., Conclusions: These results are in agreement with previously observed decrease of corticosterone clearance rate in MSG treated animals and suggest that elevated corticosterone levels in plasma and its prolonged response to stressogenic stimulation are due to elevated corticosterone production in adrenals and lower degradation rate in the liver.

The rat G-protein-coupled receptor kinase 6 (GRK6) cDNA was cloned from rat brain tissue by a combination of reverse-transcription polymerase chain reactions (RT-PCR), based on homology to the cloned human GRK6, and rapid amplification of cDNA ends (RACE-PCR). We obtained a clone of 2817 bp with an open reading frame of 1731 bp encoding for a protein of 576 amino acids that is 96.7% identical and 97.9% similar to its human counterpart. mRNA was detectable in all brain areas examined. In addition, GRK6 was expressed in skeletal muscle, small intestine, aorta, liver, heart, lung, thymus, stomach, uterus and kidney.

The effects exposing rats to space flights of various lengths in a series of COSMOS satellites are reported based on an evaluation of plasma hormone levels and several enzyme activities in the tissues. The results after space flights are compared with those obtained from rats exposed to acute or repeated stress. Space flight induced selective morphological responses in the corticotrophs and gonadotrophs of the pituitary. Plasma levels of ACTH did not change, but plasma growth hormone and TSH levels decreased after longer space flights (>14 days), while prolactin in the plasma increased after short flights (5-7 days). Plasma corticosterone was higher after all flights. Catecholamine levels in plasma increased only after long space flights. These changes in plasma hormone levels affected the activities of enzymes involved in the amino acid metabolism of the liver and lipolysis in the adipose tissues. Norepinephrine level and catecholamine synthesizing enzyme activity in the hypothalamus did not change in flight rats. The norepinephrine content, however, decreased in several nuclei selected from the hypothalamus of flight rats. Increases in plasma insulin and glucose were noted in rats after space flight. Glucagone values in plasma remained unchanged. Comparing these results from flight rats against rats exposed to acute or repeated stress indicate that long stays in microgravity do not represent intensive stressogenic stimulus of the adrenocortical and sympathetic adrenomedullar systems, and hormone alterations observed after space flight may be due primarily to acute stressor activity resulting from a return to Earth's gravity (gravitational stress).

Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.

The effect of early weaning on insulin binding was studied in rat hepatocytes. Early weaned rats were separated from lactating females on the 18th postnatal day, control animals were maintained with dams up to the 30th day. Plasma insulin and glucose levels, insulin binding capacity of isolated hepatocytes were determined at the age of 18, 22, 30 and 120 days. In some age groups a body mass and also insulin degradation by hepatocytes were determined. A decrease of plasma insulin and glucose level was found in 22day old early weaned rats as compared to 18 day old rats and to controls of the same age. A decrease of body mass was found in early weaned rats during the first week after weaning. An increase of insulin binding was observed in hepatocytes from 18 to 30 day-old control rats. However, in early weaned animals a highly significant elevation of insulin binding capacity was found in 22 day-old rats. At the age of 30 and l20 days no significant differences in insulin binding capacity of hepatocytes between early weaned and control rats were noted. A decrease of insulin degradation was observed in 22 day-old early weaned rats. These results showed that early weaning affects the glucose homeostasis and insulin binding capacity of rat hepatocytes.

The explanation of the mechanism of the response to gravity changes is of great importance for the determination of the capacity of human subjects to adapt to the load of gravitational stress. Therefore several studies were performed to investigate the activity of endocrine system, since the hormones are involved in the regulation of physiological functions and metabolic processes. However the studies of endocrine system activity during altered gravity conditions, especially during the weightlessness are influenced by the several interventions in biomedical observations due to operational program of astronauts, wide variability in individual response and tolerance, use of extensive countermeasures, differences in the type of space missions and in the studies after landing also a hypergravity effect at landing and variability in postflight readaptation process. The significant changes of plasma insulin and glucose levels were observed in astronauts during space flights and in the first days of recovery period. In the first inflight period plasma insulin levels were increased, unchanged or decreased however after 4-5 weeks of exposure to weightlessness a decrease of insulin plasma levels were noted. After space flights an increase of plasma insulin levels were demonstrated in experimental animals and in human subjects. Since plasma insulin level is considered as most important factor involved in the regulation for insulin receptors in target tissues, an investigation of insulin receptors in various tissues was performed in rats exposed to space flight or to hypokinesia (model used for simulation of some effects of microgravity).

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.